Rheumatoid arthritis is an autoimmune disease where the immune system attacks the joints, causing swelling and stiffness. It affects around 1% of the population in the UK. Key points:
- It is more common in women and typically onset is between 30-50 years of age.
- Genetics and certain infections may play a role in development. The disease is mediated by immune cells and cytokines like TNF.
- Symptoms include symmetric joint pain, swelling and stiffness especially in the hands, feet, wrists and knees.
- Left untreated it can cause joint deformities, disability and reduced quality of life over time.
- Diagnosis involves evaluating symptoms and signs plus blood tests for rheumatoid factor and
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems. SLE most commonly affects women in their 20s and 30s. The course of SLE is unpredictable, with periods of illness alternating with remission. Common initial symptoms include fatigue, fever, joint pain, and weight changes. SLE can cause skin rashes, oral ulcers, hair loss, serositis, lung involvement including pleurisy, heart involvement such as pericarditis, and kidney disease. The prognosis for SLE has improved in recent decades due to medical advances, with survival rates of approximately 95% at 5 years and 90% at 10 years. SLE is treated symptomatically mainly with
All ACUTE LYMPHOBLASTIC LEUKEMIA BY DR MAGDI SASIcardilogy
1. The document provides information about acute lymphocytic leukemia (ALL), the most common type of cancer in children. It describes the symptoms, signs, classification, and risk factors of ALL.
2. Common symptoms of ALL include fever, fatigue, easy bruising, frequent infections, and bone/joint pain. Physical signs may include pallor, organ enlargement, and lymphadenopathy.
3. ALL is classified according to the type of lymphocytes involved (B-cell vs T-cell lineage) and cellular features. The vast majority of ALL cases involve B-cell lymphocytes. Risk factors for ALL are generally unknown for most people.
Waldenstroms macroglobulinemia DR MAGDI SASIcardilogy
Waldenstrom's macroglobulinemia is a rare cancer of the lymphatic system characterized by high levels of IgM paraprotein and bone marrow infiltration by lymphoplasmacytic cells. Symptoms are variable but commonly include fatigue, weakness, weight loss, and neuropathies. Diagnosis requires demonstration of IgM paraprotein in serum and bone marrow biopsy showing lymphoplasmacytic cells. Treatment involves chemotherapy, immunotherapy, stem cell transplant, or clinical trials as the disease has an indolent course but can cause complications related to hyperviscosity.
Detailed approach to thyroid gland and parathyroid glandscardilogy
The document discusses thyroid and parathyroid disorders, including:
- Hyperthyroidism is caused by an overproduction of thyroid hormones and can be due to Graves' disease or toxic nodules. Symptoms include weight loss, heat intolerance, tremors, palpitations, and protruding eyes.
- In Graves' disease, the thyroid is enlarged and soft, and patients may experience lid retraction, exophthalmos, eye swelling, and limitations in upward gaze. Malignant exophthalmos is a medical emergency with risk of vision loss.
- Clinical examination of the thyroid involves inspection, palpation, percussion and auscultation to evaluate for signs of enlargement, consistency
This document discusses scleroderma, a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. It defines the two main types as limited scleroderma, which affects the hands, face and forearms, and diffuse scleroderma, which affects the whole body. Raynaud's phenomenon, skin thickening, gastrointestinal issues, lung fibrosis and pulmonary hypertension are common clinical features. The document provides details on pathogenesis, prevalence, risk factors, clinical assessment criteria and organ-specific complications of scleroderma.
an overview of Lupus for journalist
Lupus has a wide spectrum of manifestation. Some mild but in most cases it has a high impact of life and quality of life
Leukaemia is a cancer of the white blood cells characterized by the overproduction of abnormal white blood cells in the bone marrow. There are four main types of leukaemia - acute lymphocytic leukaemia, chronic lymphocytic leukaemia, acute myeloid leukaemia, and chronic myeloid leukaemia. The document discusses the signs, symptoms, diagnosis, and treatment for each type of leukaemia. It also covers oral manifestations that may be seen and dental management considerations for patients with leukaemia.
This patient has systemic sclerosis for 3.5 years with tight skin on hands and face, pain in knees and feet, and morning stiffness. He has multiple medical issues including renal failure and is wheelchair-bound. Examination found tight skin on hands and face. His current management includes physiotherapy, wax, and treatment for his other conditions. Further tests are needed to monitor his systemic sclerosis and complications.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems. SLE most commonly affects women in their 20s and 30s. The course of SLE is unpredictable, with periods of illness alternating with remission. Common initial symptoms include fatigue, fever, joint pain, and weight changes. SLE can cause skin rashes, oral ulcers, hair loss, serositis, lung involvement including pleurisy, heart involvement such as pericarditis, and kidney disease. The prognosis for SLE has improved in recent decades due to medical advances, with survival rates of approximately 95% at 5 years and 90% at 10 years. SLE is treated symptomatically mainly with
All ACUTE LYMPHOBLASTIC LEUKEMIA BY DR MAGDI SASIcardilogy
1. The document provides information about acute lymphocytic leukemia (ALL), the most common type of cancer in children. It describes the symptoms, signs, classification, and risk factors of ALL.
2. Common symptoms of ALL include fever, fatigue, easy bruising, frequent infections, and bone/joint pain. Physical signs may include pallor, organ enlargement, and lymphadenopathy.
3. ALL is classified according to the type of lymphocytes involved (B-cell vs T-cell lineage) and cellular features. The vast majority of ALL cases involve B-cell lymphocytes. Risk factors for ALL are generally unknown for most people.
Waldenstroms macroglobulinemia DR MAGDI SASIcardilogy
Waldenstrom's macroglobulinemia is a rare cancer of the lymphatic system characterized by high levels of IgM paraprotein and bone marrow infiltration by lymphoplasmacytic cells. Symptoms are variable but commonly include fatigue, weakness, weight loss, and neuropathies. Diagnosis requires demonstration of IgM paraprotein in serum and bone marrow biopsy showing lymphoplasmacytic cells. Treatment involves chemotherapy, immunotherapy, stem cell transplant, or clinical trials as the disease has an indolent course but can cause complications related to hyperviscosity.
Detailed approach to thyroid gland and parathyroid glandscardilogy
The document discusses thyroid and parathyroid disorders, including:
- Hyperthyroidism is caused by an overproduction of thyroid hormones and can be due to Graves' disease or toxic nodules. Symptoms include weight loss, heat intolerance, tremors, palpitations, and protruding eyes.
- In Graves' disease, the thyroid is enlarged and soft, and patients may experience lid retraction, exophthalmos, eye swelling, and limitations in upward gaze. Malignant exophthalmos is a medical emergency with risk of vision loss.
- Clinical examination of the thyroid involves inspection, palpation, percussion and auscultation to evaluate for signs of enlargement, consistency
This document discusses scleroderma, a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. It defines the two main types as limited scleroderma, which affects the hands, face and forearms, and diffuse scleroderma, which affects the whole body. Raynaud's phenomenon, skin thickening, gastrointestinal issues, lung fibrosis and pulmonary hypertension are common clinical features. The document provides details on pathogenesis, prevalence, risk factors, clinical assessment criteria and organ-specific complications of scleroderma.
an overview of Lupus for journalist
Lupus has a wide spectrum of manifestation. Some mild but in most cases it has a high impact of life and quality of life
Leukaemia is a cancer of the white blood cells characterized by the overproduction of abnormal white blood cells in the bone marrow. There are four main types of leukaemia - acute lymphocytic leukaemia, chronic lymphocytic leukaemia, acute myeloid leukaemia, and chronic myeloid leukaemia. The document discusses the signs, symptoms, diagnosis, and treatment for each type of leukaemia. It also covers oral manifestations that may be seen and dental management considerations for patients with leukaemia.
This patient has systemic sclerosis for 3.5 years with tight skin on hands and face, pain in knees and feet, and morning stiffness. He has multiple medical issues including renal failure and is wheelchair-bound. Examination found tight skin on hands and face. His current management includes physiotherapy, wax, and treatment for his other conditions. Further tests are needed to monitor his systemic sclerosis and complications.
Agranulocytosis is a condition characterized by a severe lack of neutrophils, a type of white blood cell important for fighting infections. It can be congenital or acquired through certain medications, medical procedures, or diseases. Symptoms include fever, sore throat, mouth sores, and bleeding gums. Diagnosis is made through a blood test showing very low neutrophil counts. Treatment focuses on managing infection risk through antibiotics, removing the cause if it is a drug, and using colony-stimulating factors or transplants in severe cases.
This document summarizes information about systemic sclerosis (SSc), including its definition, classification, epidemiology, etiology, pathophysiology, clinical manifestations, diagnostic criteria, management, and treatment. SSc is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. It can be classified as limited or diffuse cutaneous SSc depending on the extent of skin involvement. Common clinical features include Raynaud's phenomenon, skin thickening, joint/muscle involvement, and interstitial lung disease. Treatment focuses on managing symptoms, preventing complications, suppressing the immune system, and detecting/treating organ involvement early. New treatments targeting the fibrotic process are showing promise.
The document provides an overview of systemic lupus erythematosus (SLE) for medical students. It defines SLE, discusses its epidemiology and pathophysiology. It then describes the clinical presentation of SLE including cutaneous, musculoskeletal, serosal, renal, neurological, and hematological manifestations. It also covers investigations such as autoantibody tests and renal biopsy. Finally, it discusses lupus nephritis as a serious complication of SLE. The document aims to ensure students understand the definition, clinical picture, classification criteria, investigations, prognosis, complications and treatment approaches for SLE.
This document discusses leukemias and provides information about leukemoid reactions. It defines a leukemoid reaction as a high white blood cell count with neutrophilia usually in response to infection, which can mimic chronic myelogenous leukemia or acute myeloid leukemia. The document notes that serum leukocyte alkaline phosphatase is normally elevated in leukemoid reactions, distinguishing it from CML where it is depressed. Features suggesting a leukemoid reaction rather than leukemia include toxic granulation, a high LAP score, and an obvious cause of the neutrophilia such as infection. The document provides several potential causes of leukemoid reactions and discusses methods for distinguishing leukemoid reactions from leukemia.
Leukocytosis is an increased white blood cell count in the blood. There are five main types: neutrophilia, lymphocytosis, monocytosis, eosinophilia, and basophilia. Neutrophilia is most common and usually due to bacterial infection. Eosinophilia can be caused by allergic disorders, parasites, and some cancers. Lymphocytosis is seen with viral infections and lymphomas. Leukopenia and neutropenia involve decreased white blood cell and neutrophil counts respectively, increasing infection risk. Lymphoma involves abnormal lymphocyte proliferation. Leukemia includes acute and chronic forms, with acute being more aggressive and involving immature cells.
Leukemia is a cancer of the blood and bone marrow that results in an abnormal increase of immature white blood cells. The main types are acute and chronic leukemias, which are further classified as lymphocytic or myeloid. Symptoms can include fatigue, fever, bone/joint pain, and easy bruising/bleeding. Risk factors include age, genetics, radiation exposure, and viruses. Diagnosis involves blood tests, bone marrow biopsy, and other exams. Treatment may include chemotherapy, radiation, stem cell transplant, or targeted therapies. Some herbal treatments like garlic, licorice root, and turmeric may help due to anti-cancer properties.
This case describes a patient with limited scleroderma (CREST syndrome). Key features include:
- A 50-year-old female with CREST syndrome characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
- She is positive for the autoantibody anti-centromere, which is seen in 70-80% of limited scleroderma/CREST syndrome cases.
- Her disease involves skin thickening distal to the elbows and knees (sclerodactyly), as well as gastrointestinal symptoms of esophageal dysmotility. She has minimal organ involvement typical of limited
Leukemia is a type of cancer that affects the blood and bone marrow. It is characterized by an abnormal increase of immature white blood cells called blasts. There are several types of leukemia categorized by how quickly the disease develops (chronic or acute) and what type of blood cell is affected (lymphoid or myeloid cells). The diagnosis of leukemia often occurs after a routine blood test shows an abnormal blood cell count. Doctors use additional tests like biopsies of bone marrow or spinal fluid, cytogenetics testing, and imaging scans to determine the specific type of leukemia present.
Mixed connective tissue disease (MCTD) is a rare autoimmune disorder characterized by features of lupus, scleroderma, and polymyositis. It most often affects women in their 20s and 30s. While the cause is unknown, the immune system mistakenly attacks healthy connective tissue. Diagnosis is based on signs and symptoms as well as the presence of specific antibodies. Treatment focuses on managing symptoms and may include corticosteroids.
Leukemia is a malignant hematologic disorder characterized by a proliferation of abnormal white blood cells. It was first described in the 1800s and results from genetic mutations that allow abnormal cells to proliferate. The main types are acute and chronic leukemias, which are further classified as myeloid or lymphoid. Common symptoms include fatigue, weakness, bleeding, and infection. Diagnosis involves blood tests, bone marrow examination, immunophenotyping, cytogenetics, and molecular studies to determine the specific subtype and proper treatment.
The document discusses acute lymphoblastic leukemia (ALL), which is the most common childhood leukemia. It makes up around 80% of childhood leukemia cases. The document covers the introduction, classification, etiology, diagnosis, clinical presentation, and treatment of ALL. It notes that the cure rate for ALL is around 85% with current treatments involving remission induction, intensification, and maintenance therapy. Prognosis depends on factors like age, white blood cell count at diagnosis, and the ALL subtype.
A middle-aged woman presented with generalized weakness, rashes, and sores. On examination, she had hyperpigmentation, edema, and rashes on her buttocks and groin. Tests found elevated muscle enzymes. She was diagnosed with dermatomyositis and admitted for IV fluids and steroids. Her symptoms worsened, and she developed difficulty raising her arms, confirming the diagnosis of dermatomyositis. She was started on immunosuppressants and referred for palliative care.
This document provides information about acute lymphoblastic leukemia (ALL). It discusses that ALL is a cancer of the lymphoid cells that is most common in children. The document covers the classification, immunologic subtypes, cytogenetic abnormalities, clinical features, diagnostic measures, and hematological and histological findings of ALL. It describes that ALL is diagnosed based on complete blood count, peripheral smear, bone marrow biopsy and cytogenetic/flow cytometry analysis. The key diagnostic findings include anemia, leukocytosis, thrombocytopenia and lymphoblasts in the bone marrow.
Cancer is characterized by uncontrolled cell growth and spread. Leukemia is a type of cancer that affects the blood and bone marrow. It is caused by abnormal white blood cells that do not function properly. Symptoms include fatigue, weakness, and susceptibility to infections due to low blood cell counts. Risk factors include radiation, chemicals, viruses, and genetic predispositions. Researchers are studying interactions between molecules like STAT3 and PRL-3 that may contribute to acute myeloid leukemia's development and could be potential treatment targets. Current treatments include chemotherapy, radiation, stem cell transplants, and some herbal remedies.
This document provides information on sarcoidosis, a disease characterized by the growth of granulomas in multiple organs of the body. It begins by discussing the causes of sarcoidosis, which is an immune reaction that continues even after the initial trigger is cleared. Common areas affected include the lungs, eyes, skin, and lymph nodes. The stages of pulmonary sarcoidosis and associated symptoms are described. Treatment options are outlined, ranging from symptomatic treatment for mild cases to corticosteroids and immunosuppressants for more severe symptoms.
Leukaemia is a cancer of the blood cells that can be acute or chronic. It involves overproduction of either lymphocytes or myelocytes. Treatment aims to induce remission through chemotherapy then maintain remission, but prognosis remains poor compared to other cancers, with less than half of patients surviving more than 5 years.
Leukemia is a cancer that affects the blood and bone marrow. It causes the body to produce immature white blood cells that do not function properly. There are four main types of leukemia - acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia. Management of leukemia involves chemotherapy, targeted therapy, radiation therapy or stem cell transplant depending on the type and stage of leukemia. The goal of treatment is to destroy signs of leukemia in the body and induce remission.
This document provides detailed information on polycythemia vera (PV), including its pathophysiology, clinical features, diagnosis, differential diagnosis, and laboratory evaluation. PV is a myeloproliferative neoplasm characterized by excessive red blood cell production. Key points: PV results from abnormal stem cell clone producing increased red blood cells, white blood cells, and platelets. Symptoms include bleeding, thrombosis, pruritus, headache, and visual issues due to hyperviscosity. Diagnosis requires elevated red blood cell count/mass and meeting criteria set by the Polycythemia Vera Study Group or WHO guidelines, which may include genetic testing for JAK2 mutation. Differential diagnosis excludes secondary causes of polycy
1. Bronchogenic carcinoma is lung cancer that arises from the bronchial epithelium. Symptoms include new or changing cough, dyspnea, hemoptysis, weight loss, and chest abnormalities on imaging.
2. Risk factors include cigarette smoking, asbestos exposure, and family history. Histologically, the main types are small cell lung carcinoma and non-small cell lung carcinoma (NSCLC).
3. NSCLC makes up about 80% of cases and may be surgically resected if localized. Small cell lung carcinoma tends to spread early and is usually treated with chemotherapy or chemoradiation. Staging evaluates tumor size, lymph node involvement, and metastasis using the TNM system.
Agranulocytosis is a condition characterized by a severe lack of neutrophils, a type of white blood cell important for fighting infections. It can be congenital or acquired through certain medications, medical procedures, or diseases. Symptoms include fever, sore throat, mouth sores, and bleeding gums. Diagnosis is made through a blood test showing very low neutrophil counts. Treatment focuses on managing infection risk through antibiotics, removing the cause if it is a drug, and using colony-stimulating factors or transplants in severe cases.
This document summarizes information about systemic sclerosis (SSc), including its definition, classification, epidemiology, etiology, pathophysiology, clinical manifestations, diagnostic criteria, management, and treatment. SSc is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. It can be classified as limited or diffuse cutaneous SSc depending on the extent of skin involvement. Common clinical features include Raynaud's phenomenon, skin thickening, joint/muscle involvement, and interstitial lung disease. Treatment focuses on managing symptoms, preventing complications, suppressing the immune system, and detecting/treating organ involvement early. New treatments targeting the fibrotic process are showing promise.
The document provides an overview of systemic lupus erythematosus (SLE) for medical students. It defines SLE, discusses its epidemiology and pathophysiology. It then describes the clinical presentation of SLE including cutaneous, musculoskeletal, serosal, renal, neurological, and hematological manifestations. It also covers investigations such as autoantibody tests and renal biopsy. Finally, it discusses lupus nephritis as a serious complication of SLE. The document aims to ensure students understand the definition, clinical picture, classification criteria, investigations, prognosis, complications and treatment approaches for SLE.
This document discusses leukemias and provides information about leukemoid reactions. It defines a leukemoid reaction as a high white blood cell count with neutrophilia usually in response to infection, which can mimic chronic myelogenous leukemia or acute myeloid leukemia. The document notes that serum leukocyte alkaline phosphatase is normally elevated in leukemoid reactions, distinguishing it from CML where it is depressed. Features suggesting a leukemoid reaction rather than leukemia include toxic granulation, a high LAP score, and an obvious cause of the neutrophilia such as infection. The document provides several potential causes of leukemoid reactions and discusses methods for distinguishing leukemoid reactions from leukemia.
Leukocytosis is an increased white blood cell count in the blood. There are five main types: neutrophilia, lymphocytosis, monocytosis, eosinophilia, and basophilia. Neutrophilia is most common and usually due to bacterial infection. Eosinophilia can be caused by allergic disorders, parasites, and some cancers. Lymphocytosis is seen with viral infections and lymphomas. Leukopenia and neutropenia involve decreased white blood cell and neutrophil counts respectively, increasing infection risk. Lymphoma involves abnormal lymphocyte proliferation. Leukemia includes acute and chronic forms, with acute being more aggressive and involving immature cells.
Leukemia is a cancer of the blood and bone marrow that results in an abnormal increase of immature white blood cells. The main types are acute and chronic leukemias, which are further classified as lymphocytic or myeloid. Symptoms can include fatigue, fever, bone/joint pain, and easy bruising/bleeding. Risk factors include age, genetics, radiation exposure, and viruses. Diagnosis involves blood tests, bone marrow biopsy, and other exams. Treatment may include chemotherapy, radiation, stem cell transplant, or targeted therapies. Some herbal treatments like garlic, licorice root, and turmeric may help due to anti-cancer properties.
This case describes a patient with limited scleroderma (CREST syndrome). Key features include:
- A 50-year-old female with CREST syndrome characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
- She is positive for the autoantibody anti-centromere, which is seen in 70-80% of limited scleroderma/CREST syndrome cases.
- Her disease involves skin thickening distal to the elbows and knees (sclerodactyly), as well as gastrointestinal symptoms of esophageal dysmotility. She has minimal organ involvement typical of limited
Leukemia is a type of cancer that affects the blood and bone marrow. It is characterized by an abnormal increase of immature white blood cells called blasts. There are several types of leukemia categorized by how quickly the disease develops (chronic or acute) and what type of blood cell is affected (lymphoid or myeloid cells). The diagnosis of leukemia often occurs after a routine blood test shows an abnormal blood cell count. Doctors use additional tests like biopsies of bone marrow or spinal fluid, cytogenetics testing, and imaging scans to determine the specific type of leukemia present.
Mixed connective tissue disease (MCTD) is a rare autoimmune disorder characterized by features of lupus, scleroderma, and polymyositis. It most often affects women in their 20s and 30s. While the cause is unknown, the immune system mistakenly attacks healthy connective tissue. Diagnosis is based on signs and symptoms as well as the presence of specific antibodies. Treatment focuses on managing symptoms and may include corticosteroids.
Leukemia is a malignant hematologic disorder characterized by a proliferation of abnormal white blood cells. It was first described in the 1800s and results from genetic mutations that allow abnormal cells to proliferate. The main types are acute and chronic leukemias, which are further classified as myeloid or lymphoid. Common symptoms include fatigue, weakness, bleeding, and infection. Diagnosis involves blood tests, bone marrow examination, immunophenotyping, cytogenetics, and molecular studies to determine the specific subtype and proper treatment.
The document discusses acute lymphoblastic leukemia (ALL), which is the most common childhood leukemia. It makes up around 80% of childhood leukemia cases. The document covers the introduction, classification, etiology, diagnosis, clinical presentation, and treatment of ALL. It notes that the cure rate for ALL is around 85% with current treatments involving remission induction, intensification, and maintenance therapy. Prognosis depends on factors like age, white blood cell count at diagnosis, and the ALL subtype.
A middle-aged woman presented with generalized weakness, rashes, and sores. On examination, she had hyperpigmentation, edema, and rashes on her buttocks and groin. Tests found elevated muscle enzymes. She was diagnosed with dermatomyositis and admitted for IV fluids and steroids. Her symptoms worsened, and she developed difficulty raising her arms, confirming the diagnosis of dermatomyositis. She was started on immunosuppressants and referred for palliative care.
This document provides information about acute lymphoblastic leukemia (ALL). It discusses that ALL is a cancer of the lymphoid cells that is most common in children. The document covers the classification, immunologic subtypes, cytogenetic abnormalities, clinical features, diagnostic measures, and hematological and histological findings of ALL. It describes that ALL is diagnosed based on complete blood count, peripheral smear, bone marrow biopsy and cytogenetic/flow cytometry analysis. The key diagnostic findings include anemia, leukocytosis, thrombocytopenia and lymphoblasts in the bone marrow.
Cancer is characterized by uncontrolled cell growth and spread. Leukemia is a type of cancer that affects the blood and bone marrow. It is caused by abnormal white blood cells that do not function properly. Symptoms include fatigue, weakness, and susceptibility to infections due to low blood cell counts. Risk factors include radiation, chemicals, viruses, and genetic predispositions. Researchers are studying interactions between molecules like STAT3 and PRL-3 that may contribute to acute myeloid leukemia's development and could be potential treatment targets. Current treatments include chemotherapy, radiation, stem cell transplants, and some herbal remedies.
This document provides information on sarcoidosis, a disease characterized by the growth of granulomas in multiple organs of the body. It begins by discussing the causes of sarcoidosis, which is an immune reaction that continues even after the initial trigger is cleared. Common areas affected include the lungs, eyes, skin, and lymph nodes. The stages of pulmonary sarcoidosis and associated symptoms are described. Treatment options are outlined, ranging from symptomatic treatment for mild cases to corticosteroids and immunosuppressants for more severe symptoms.
Leukaemia is a cancer of the blood cells that can be acute or chronic. It involves overproduction of either lymphocytes or myelocytes. Treatment aims to induce remission through chemotherapy then maintain remission, but prognosis remains poor compared to other cancers, with less than half of patients surviving more than 5 years.
Leukemia is a cancer that affects the blood and bone marrow. It causes the body to produce immature white blood cells that do not function properly. There are four main types of leukemia - acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia. Management of leukemia involves chemotherapy, targeted therapy, radiation therapy or stem cell transplant depending on the type and stage of leukemia. The goal of treatment is to destroy signs of leukemia in the body and induce remission.
This document provides detailed information on polycythemia vera (PV), including its pathophysiology, clinical features, diagnosis, differential diagnosis, and laboratory evaluation. PV is a myeloproliferative neoplasm characterized by excessive red blood cell production. Key points: PV results from abnormal stem cell clone producing increased red blood cells, white blood cells, and platelets. Symptoms include bleeding, thrombosis, pruritus, headache, and visual issues due to hyperviscosity. Diagnosis requires elevated red blood cell count/mass and meeting criteria set by the Polycythemia Vera Study Group or WHO guidelines, which may include genetic testing for JAK2 mutation. Differential diagnosis excludes secondary causes of polycy
1. Bronchogenic carcinoma is lung cancer that arises from the bronchial epithelium. Symptoms include new or changing cough, dyspnea, hemoptysis, weight loss, and chest abnormalities on imaging.
2. Risk factors include cigarette smoking, asbestos exposure, and family history. Histologically, the main types are small cell lung carcinoma and non-small cell lung carcinoma (NSCLC).
3. NSCLC makes up about 80% of cases and may be surgically resected if localized. Small cell lung carcinoma tends to spread early and is usually treated with chemotherapy or chemoradiation. Staging evaluates tumor size, lymph node involvement, and metastasis using the TNM system.
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that is not fully reversible. The two main conditions that cause COPD are chronic bronchitis and emphysema. Chronic bronchitis involves a long-term cough with mucus, while emphysema involves destruction of lung tissue leading to fewer and larger air spaces. The primary risk factor is cigarette smoking. Symptoms include cough, sputum production, wheezing and shortness of breath. Diagnosis is made based on history of symptoms and spirometry showing airflow limitation. Treatment focuses on smoking cessation and medications to relieve symptoms.
The document discusses pleural effusion, including its normal physiology, pathogenesis, clinical manifestations, aetiology, investigations, and medical management. Pleural effusion occurs when fluid formation in the pleural space increases or absorption decreases, causing fluid accumulation. Effusions can be transudative or exudative. Investigations include chest x-ray, ultrasound, and thoracentesis for diagnostic and therapeutic purposes. Management involves treating the underlying cause, therapeutic thoracentesis for symptom relief, and procedures for recurrent or complicated effusions.
Primary myelofibrosis (PMF) is a chronic blood cancer characterized by excessive scar tissue in the bone marrow that impairs blood cell production. It typically affects people over age 50 and common symptoms include fatigue, abdominal pain or fullness from an enlarged spleen or liver, and easy bruising or bleeding from low blood cell counts. The disease is diagnosed based on physical signs of splenomegaly, blood tests showing low blood cell counts and abnormal cells, and examination of the bone marrow showing increased fibrosis.
ULCEARTIVE COLITIS DIAGNOSIS AND TRAETMENTBY MAGDI SASI 2015cardilogy
Ulcerative colitis is a form of inflammatory bowel disease that causes inflammation and ulcers in the lining of the rectum and colon. It typically presents with bloody diarrhea, abdominal pain, and urgency. The disease involves continuous inflammation starting in the rectum and varies in extent from distal colitis to pancolitis. It is associated with extra-intestinal manifestations affecting the skin, eyes, joints, and liver. The cause is unknown but may involve genetic factors and abnormal immune response. Treatment depends on the severity and extent of disease.
The document provides detailed information about acute myeloblastic leukemia (AML), including its definition, classification, symptoms, incidence, characteristics, and morphological subtypes. AML is a cancer of the blood and bone marrow characterized by rapid proliferation of immature blast cells. It is the most common type of acute leukemia in adults. The document discusses the French-American-British classification system and the World Health Organization classification system for AML and its various subtypes.
This document discusses portal hypertension and esophageal varices. It begins by defining portal hypertension as increased blood pressure within the portal venous system, usually caused by cirrhosis of the liver obstructing blood flow. Esophageal varices develop as collateral blood vessels when portal pressure exceeds 12 mmHg. The document then covers causes of portal hypertension, risk factors for bleeding varices, clinical presentation, investigations including endoscopy, and treatment approaches focusing on preventing or managing bleeding from varices.
Detaliled approach to ascitic patients in liver cirrhosiscardilogy
This document provides detailed information on ascites, including causes, mechanisms, diagnosis, and complications. It discusses that ascites is generally caused by cirrhosis in 85% of cases and results from salt and water retention due to increased aldosterone levels and increased lymph formation from sinusoidal hypertension. Diagnosis involves paracentesis to examine ascitic fluid and measure factors like white blood cell count to check for spontaneous bacterial peritonitis. Complications of ascites include infections, hemorrhage, and spontaneous bacterial peritonitis.
1. Acute renal failure (ARF) can be caused by pre-renal factors which decrease blood flow to the kidneys (75% of cases), renal damage to the kidney parenchyma itself (10-20% of cases), or post-renal obstruction of urine flow (2-15% of cases).
2. Common causes of pre-renal ARF include hypovolemia, decreased cardiac output, sepsis, renal artery occlusion, and certain drugs. Renal causes include various types of glomerulonephritis, interstitial nephritis caused by drugs and infections, and acute tubular necrosis from ischemia or toxins. Post-renal ARF can be due to
1. Examine the general appearance of the patient including height, weight, build, position in bed, and level of consciousness. Note any pallor, cyanosis, jaundice, clubbing, edema.
2. Examine the neck for jugular venous pulse, thyroid enlargement, lymph nodes. Position the patient semi-sitting and inspect for distention of neck veins above the clavicle.
3. Inspect the hands and nails for signs of anemia, cyanosis, clubbing and examine the conjunctiva for pallor, jaundice or hemorrhages. Ask the patient to look up and down to examine the sclera and conjunctiva fully.
The document appears to contain the name "Magdi Awad Sasi" along with the year "2013". It does not provide any other context or information beyond this name and date. In just two words, the document lists a name and year without any other details that could provide meaningful context or insight into its purpose or content.
- Acute renal failure (ARF) is a sudden decline in kidney function that develops over hours or days. It can have pre-renal, intrinsic renal, or post-renal causes.
- Intrinsic renal ARF, also called acute tubular necrosis (ATN), is caused by direct injury to the kidneys and accounts for 30-50% of cases. ATN can be ischemic, due to low blood flow, or toxic, caused by substances damaging to the kidneys.
- Diagnosis involves evaluating blood tests, urine tests, and medical history for clues to the underlying cause. Urine osmolality and urine sodium levels can help distinguish between pre-renal, intrinsic renal
TO THE SOUL OF THE PEOPLE WHO DREAMS BETTER DAYS AND PERFECT FUTURE WHO DIED THINKING THAT LIBYA IS WORTHY NOT THE LIBYAN
HOPPING OUR ALLAH ACCEPT THIS SMALL WORK
Botulism is caused by a toxin produced by the bacterium Clostridium botulinum. It is a rare but serious illness that causes muscle paralysis. There are three main types - foodborne, wound, and infant botulism. Foodborne botulism results from eating contaminated food while infant botulism occurs when an infant ingests botulinum spores. Symptoms include blurred vision, difficulty swallowing and speaking, and descending paralysis. Diagnosis involves culture testing of suspect foods, stool, or throat samples to identify the bacteria. Prompt treatment is needed to prevent respiratory failure.
A 40-year-old female presented with 1 year of bilateral symmetrical arthritis of hand joints, wrists, elbows and toes with morning stiffness lasting 4 hours. On examination, she had pallor and arthritis of involved joints but no deformities. The most likely diagnosis is rheumatoid arthritis (RA). RA is the best fitting diagnosis given the symmetrical polyarthritis and absence of features suggesting other diagnoses.
A key diagnostic test for RA is anti-cyclic citrullinated peptide antibody (anti-CCP Ab) as it is highly specific for the disease. Normocytic normochromic anemia is an indicator of disease activity in RA. Soft tissue swelling but not bony ankylosis may be seen
1. Aortic dissection is a tear in the inner layer of the aorta that allows blood to flow between the layers, causing severe chest pain. It is a medical emergency with high mortality if left untreated.
2. Diagnosis is based on symptoms of sudden, severe chest pain and imaging tests like CT scan or MRI that can detect the tear and blood flow between the layers of the aorta.
3. Risk factors include high blood pressure, genetic connective tissue disorders, injuries to the chest, and pregnancy. Prompt diagnosis and treatment are needed to prevent death.
1. Acute coronary syndrome (ACS) refers to a range of conditions caused by reduced blood flow in the coronary arteries, including unstable angina and myocardial infarction (heart attack).
2. ACS is classified based on ECG findings into ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina. The most common symptoms are chest pain and discomfort.
3. Diagnosis involves evaluating the patient's history, symptoms, ECG, and cardiac biomarker levels. Together these can confirm if myocardial necrosis has occurred. Treatment depends on the classification but generally involves antiplatelet agents, statins, and revascularization if indicated.
ACUTE RESPIRATORY FAILURE MAGDI SASI 2015cardilogy
1. Acute respiratory failure is defined as a severe form of respiratory insufficiency resulting in a PaO2 of less than 60 mmHg or a PaCO2 of more than 50 mmHg.
2. There are two main types - type 1 with low PaO2 and normal or low PaCO2, and type 2 with low PaO2 and high PaCO2.
3. Major causes include diffuse airway obstruction, central airway obstruction, restrictive lung disease, pulmonary vascular disease, pleural and chest wall diseases, and neuromuscular diseases.
This document provides an overview of rheumatoid arthritis (RA), including its definition, incidence, risk factors, clinical presentation, investigations, diagnosis, and treatment. RA is a chronic inflammatory disease that primarily affects the joints, most commonly in the hands, feet and wrists. It occurs in around 3% of adults and is more common in females. Genetic and environmental factors are involved in its pathogenesis. Clinically, it presents with symmetric joint swelling, stiffness, and can involve extra-articular structures. Investigations include blood tests and x-rays. Treatment aims to control symptoms, prevent joint damage, and involves medications like DMARDs and biologics, as well as physical therapy and surgery.
Rhematoid arthritis is systemic autoimmune inflammatory disorder of unknown etiology affecting multiple organ systems. These ppt includes comprehensive management of it.
Rheumatoid arthritis is a chronic inflammatory disease characterized by symmetric polyarthritis of unknown etiology, predominantly affecting small joints. It is more prevalent in women, with onset typically in the 4th-5th decade in women and 6th-8th decade in men. Genetics play a role, as it is more common in twins and relatives of those diagnosed. Environmental factors like smoking and infections may also influence susceptibility. The disease process involves immune cells infiltrating joints and releasing proinflammatory cytokines, promoting swelling of synovial membranes and destruction of cartilage and bone. This leads to characteristic joint deformities if left uncontrolled over time.
Rheumatoid arthritis is a chronic inflammatory disease that predominantly affects the joints, with peak incidence between ages 40-60. It is characterized by symmetric polyarticular involvement of small joints like the hands and feet. Osteoarthritis is the most common type of arthritis and is characterized by cartilage breakdown in the joints leading to pain and stiffness. Gout is caused by deposition of uric acid crystals in the joints and tissues, causing inflammatory attacks of monoarticular arthritis, often in the big toe.
A case presentation on juvenile idiopathic arthritisDr. Tanvir
This document provides an overview of juvenile idiopathic arthritis (JIA), including its etiology, pathophysiology, classification, clinical manifestations, diagnosis, complications, treatment, and follow up. JIA is the most common chronic rheumatic illness in children, characterized by synovitis and inflammation of peripheral joints. While its exact cause is unknown, it involves both genetic and environmental factors. Treatment involves a multidisciplinary approach including medications like NSAIDs, DMARDs, steroids, and biologics, as well as physiotherapy, with the goals of relieving symptoms, slowing disease progression, and preserving joint function.
Juvenile Idiopathic Arthritis (JIA) is defined as arthritis of unknown cause that begins before age 16 and lasts over 6 weeks. It is classified based on symptoms into subtypes including systemic onset JIA, oligoarticular JIA, and polyarticular JIA. Treatment involves a stepwise approach starting with NSAIDs and intra-articular steroids and escalating to DMARDs and biologicals. Complications can include chronic anterior uveitis, osteoporosis, and potentially life-threatening macrophage activation syndrome.
This document provides information on rheumatoid arthritis (RA), including its presentation, pathogenesis, diagnostic criteria, management, and complications. Some key points:
- RA is a chronic inflammatory disease that primarily affects the joints in a symmetrical pattern. It has an unknown cause but is associated with certain genetic factors.
- Diagnosis is based on symptoms lasting over 6 weeks involving at least 3 joint areas. Serological markers and imaging can help with diagnosis. Untreated, it can lead to long-term joint damage and disability.
- Management involves early use of disease-modifying antirheumatic drugs (DMARDs) like methotrexate to reduce inflammation and prevent joint damage. Biologics may be
Rheumatoid arthritis is a systemic inflammatory disease that commonly affects the small joints of the hands and feet. It is characterized by symmetric polyarthritis, constitutional symptoms, rheumatoid nodules, and can involve various organ systems. Early diagnosis is important to prevent long-term joint damage and complications. The pathogenesis involves autoimmune processes leading to inflammation of the synovial membranes of joints. Diagnosis is based on clinical features and confirmation with serological markers such as rheumatoid factor and anti-CCP antibodies.
Acute rheumatic fever-definition,pathophysiology,clinical presentation and ma...onlinefreelancer1
A detailed approach to ACUTE RHEUMATIC FEVER,based on Harrison Principles of internal medicine and Braunwald Textbook of Cardiology.Useful for post graduate seminars.
Rheumatoid arthritis is a chronic systemic inflammatory disease that causes swelling, stiffness, and pain in the joints. It is characterized by periods of disease flares and remissions. The cause is unknown but genetic and environmental factors are believed to play a role. It often affects the small joints in a symmetrical pattern and can lead to deformity and loss of function over time if not properly treated. Complications can include joint damage, tendon rupture, lung or heart inflammation, and in rare cases, amyloidosis.
This document provides information on rheumatoid arthritis (RA), including its presentation, pathogenesis, diagnostic criteria, management, and complications. Some key points:
- RA is a chronic inflammatory disease that primarily affects the joints in a symmetrical pattern. It has an unknown cause but is associated with certain genetic factors. Left untreated, it can cause long-term joint damage and disability.
- Diagnosis is based on symptoms lasting over 6 weeks in multiple joints as well as laboratory findings like elevated inflammatory markers and autoantibodies. Imaging can detect early bone erosions not seen on x-rays.
- Treatment aims to induce and maintain remission to prevent joint damage, with a treat-to-target approach. This
Definitions, Epidemiology, Etiology, Pathophysiology, Clinical presentation/Clinical features/Signs & Symptoms, Diagnosis, Treatment: Non pharmacological treatment and Pharmacological treatment. All you need to know about Rheumatoid Arthritis. References. Pharm D 3rd year syllabus.
Rheumatoid arthritis is a chronic progressive inflammatory disease that affects the joints, most commonly in the hands and feet. It is more common in women and usually develops between the ages of 20-40. Symptoms include pain, swelling, stiffness, and loss of function in multiple symmetrical joints. If left untreated, it can cause permanent joint damage and deformity. Treatment involves medications to reduce inflammation and slow disease progression, as well as physical therapy and exercises to maintain joint mobility and function.
Rheumatoid arthritis is an autoimmune disorder where the immune system attacks the synovial membrane lining the joints, causing inflammation. It commonly first affects small joints in the hands and can lead to joint deformity, damage, and disability over time. Treatments include medications like NSAIDs, DMARDs, steroids and biologics, as well as exercise and surgery. Ankylosing spondylitis is a related inflammatory arthritis that primarily affects the spine, causing fusion of vertebrae and a stooped posture. It has genetic and environmental risk factors and is treated with exercise, NSAIDs, and biologics. Graft-versus-host disease occurs when donor immune cells in a bone marrow transplant attack
Rheumatoid arthritis is a chronic inflammatory disease that causes pain, stiffness, and swelling in the joints. It occurs when the immune system mistakenly attacks the joints, causing inflammation and damage over time. Common symptoms include pain and stiffness in the small joints of the hands and feet that is usually worse in the morning. If not treated early, rheumatoid arthritis can lead to joint deformity and increased disability. The cause is unknown but is believed to involve genetic and environmental factors. Diagnosis involves physical exam, blood tests for rheumatoid factor and anti-CCP antibodies, and x-rays of affected joints.
Psoriatic arthritis is a chronic inflammatory disease that affects the joints and skin. It is characterized by osteolysis, bony proliferation, and can cause dactylitis, enthesitis, spondylitis, and various forms of arthritis. While it is classified as a type of spondyloarthritis, it is distinct from rheumatoid arthritis in that it is usually seronegative. The presentation and pattern of joint involvement in psoriatic arthritis can vary between patients and change over time, with the most common forms being asymmetrical oligoarthritis or symmetrical polyarthritis. Diagnosis is based on clinical features and classification criteria such as the CASPAR criteria.
Acute rheumatic fever is an autoimmune disease resulting from a streptococcal infection. It mainly affects children aged 5-15 and can cause polyarthritis, carditis, chorea, and skin manifestations. While most symptoms resolve, cardiac valvular damage (rheumatic heart disease) can persist. Long term antibiotic prophylaxis is needed to prevent recurrent episodes and further cardiac damage.
Psoriatic arthritis is a form of inflammatory arthritis that affects approximately 7-42% of people with psoriasis. It most commonly presents between ages 35-50 as symmetric polyarthritis or asymmetric oligoarthritis of the hands and feet that can progress to involve more joints over time. Diagnosis is based on criteria such as evidence of psoriasis, nail changes, negative rheumatoid factor, dactylitis, and radiographic evidence of new bone formation. Treatment involves NSAIDs, local steroid injections, and disease-modifying antirheumatic drugs.
Arthropathy in haematological disorders in childrendattasrisaila
This document discusses various hematological disorders that can present with rheumatological symptoms in children. It describes benign disorders like sickle cell disease, thalassemias, and hemophilia that can cause joint pain, swelling, and damage. It also covers malignant disorders like leukemic arthritis and how certain cancers like leukemia can initially manifest as musculoskeletal complaints. For each condition, it provides details on presentations, treatments, and long term complications involving the bones and joints.
Similar to RHEUMATOID ARTHRITIS --DR MAGDI SASI 2016 (20)
The document discusses peptic ulcer disease. It begins with definitions of erosion and ulcer, then covers epidemiology including higher rates in males historically but now similar rates between sexes. It discusses pathogenesis related to a balance of protective and aggressive factors, including the role of Helicobacter pylori and nonsteroidal anti-inflammatory drugs. Treatment involves eradicating H. pylori if present, reducing acid production, and supporting mucosal defenses. Complications can include perforation, bleeding and stenosis.
Motor function of brain and brain stem ms 2018 dentist MAGDI SASIcardilogy
The document discusses motor control in the brain and brain stem. It describes how movements are planned and executed at different hierarchical levels from high-level strategy down to low-level execution. Key structures involved include the motor cortex, basal ganglia, cerebellum, and brain stem. The cerebellum specifically helps coordinate voluntary movements and maintain balance. It has different functional regions including the neocerebellum, spinocerebellum, and vestibulocerebellum that control skilled distal movements, posture and proximal limb movements, and balance respectively. Diseases of these motor control structures can produce neurological abnormalities like ataxia.
Bp 2021 blood flow physiological factors magdi sasicardilogy
The document discusses blood pressure and the factors that influence it. It notes that as blood flows through smaller vessels, it meets resistance due to the vessel size and viscosity of blood. This peripheral resistance generates and maintains arterial blood pressure. Constriction of small vessels increases resistance and blood pressure, while dilation decreases resistance and pressure. The thickness of the left ventricular wall, which is greater than the right, reflects the higher pressure load on the left ventricle from pumping blood into the aorta compared to the right ventricle's lower pressure load into the pulmonary artery. Blood flows unidirectionally through the circulatory system due to heart pumping and maintenance of sufficient pressure.
Role of kidney in acid base balance saturday interactive lecture m MAGDI AWAD...cardilogy
The kidney plays a key role in regulating acid-base balance by secreting hydrogen ions (H+) and reabsorbing bicarbonate (HCO3-) ions. In the proximal convoluted tubule, for each H+ secreted, one Na+ and HCO3- are reabsorbed via active transport. In the distal convoluted tubule and collecting duct, H+ can be secreted either dependently or independently of Na+ reabsorption through formation of acid phosphates or ammonia. This preserves bicarbonate levels in the blood and buffers hydrogen ions that are excreted in urine, helping to maintain acid-base homeostasis.
The patient has pancytopenia with low white blood cell count, red blood cell count, hemoglobin, and platelet count. Possible underlying causes include bone marrow failure and hematologic malignancies. Main complications include infection due to low white blood cells and anemia.
This document provides guidance on performing a physical examination of the lungs and chest. It describes how to inspect for scars and deformities, assess tracheal position and chest expansion, palpate the apex beat, and auscultate breath sounds. Specific techniques are outlined for percussion and assessing tactile vocal fremitus. Abnormal findings are associated with conditions like pleural effusion, pneumonia, and lung abscess. The goal is a thorough evaluation of the lungs and chest to identify any underlying pathologies.
This document provides instructions for performing an abdominal examination, including techniques for palpation, percussion, and auscultation. It describes how to palpate the abdominal quadrants and specific organs like the liver and spleen. Instructions are given for percussion of the liver and checking for shifting dullness. The fluid thrill test and listening for bowel sounds and bruits are also outlined. The goal is to examine the abdominal contour, feel for masses or swelling, and check the size and position of internal organs.
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This document discusses the mechanism of respiration including:
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History series case one by magdi sasi 2020cardilogy
A 30-year-old Libyan woman presented with bilateral leg swelling for one week and progressive dyspnea for the last day. She reports the leg swelling started in her feet and progressed to her knees over one week. Her dyspnea had been gradually worsening over the past 4 months since giving birth to a healthy baby. She experiences paroxysmal nocturnal dyspnea and orthopnea. Based on her symptoms of progressive exertional dyspnea, leg swelling, and history of recent childbirth, the likely diagnosis is heart failure due to postpartum cardiomyopathy.
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The presence of ataxia suggests damage to any of the following EXCEPT:
B. Thalamus
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Glomerular disease postgraduate magdi sasi 2019cardilogy
Glomerular disease involves inflammation and damage of the glomeruli, allowing protein and blood to leak into the urine. It can present as isolated hematuria and/or proteinuria, nephrotic syndrome, nephritic syndrome, acute renal failure, or chronic renal failure. Glomerular disease is categorized as proliferative or non-proliferative and can be primary or secondary to other conditions like diabetes or lupus. Common symptoms include edema, hypertension, azotemia, and oliguria. Histologic changes in glomeruli include hypercellularity, basement membrane thickening, and sclerosis. Minimal change disease commonly causes nephrotic syndrome in children and is characterized by foot process effacement on
Chronic myeloid leukemia magdi sasi 2019 ramadancardilogy
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocytic cells without loss of differentiation capacity. It accounts for 20% of adult leukemias. Diagnosis is based on markedly elevated white blood cell count, left shifted myeloid series with low promyelocytes/blasts, and presence of the Philadelphia chromosome. CML progresses through chronic, accelerated, and blast crisis phases, with blast crisis resembling acute leukemia and carrying a poor prognosis of about 6 months.
The document summarizes key aspects of immunity and the immune system. It describes how innate and acquired immunity function, with innate immunity providing nonspecific responses and acquired immunity providing specific responses after exposure. It outlines the roles of macrophages, T cells, B cells, antibodies, and humoral versus cell-mediated responses. The lymphatic system plays an active role in immunity. Blood groups are determined by antigens on red blood cells, and transfusions require matching blood types to avoid antibody-mediated destruction of transfused cells.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
RHEUMATOID ARTHRITIS
Prevalence in UK = 1%
The incidence of rheumatoid arthritis is approximately 25 to 30 per 100 000 per
year (1.5 in men and 3.6 in women).
Prevalence ----over 65years in males 1.9% ,in females 5%
Peak onset = 30-50 years, although occurs in all age groups
F:M ratio = 3:1 Some ethnic differences e.g. high in Native Americans
Genetic --Associated with HLA-DR 1 and HLA-DR4 (especially Felty's syndrome).
RA is associated with several antibodies such as RF, collagen antibody, capable of
reaction at sites other than the joints (i.e. the disease is not confined to the joints).
Damage is mediated by several means, including macrophages activated by CD4+ T
cells, and by complement fixing immune complexes.
Age :
May present at any age
Typical age in female ----child bearing years ((late))
In male ----6th
---8th
decade
0nset:
May be Fulminant (( almost over nieght))
More commonly insidious ---weeks to months
Distribution :
At onset ,20% monoarticular disease and 80% have multiple joint involvement.
First small joints ---MCP ,MTP & PIP
Later large joints ----knees ,elbows
A number of studies have suggested a link between Proteus mirabilis infection and
the development of RA in susceptible individuals, and this may contribute to the
increased incidence of RA in women, who are more susceptible to UTI.
PATHOGENSIS:
Rheumatoid arthritis - TNF is key in pathophysiology
TNF is important in the pathogenesis of rheumatoid arthritis. TNF blockers (e.g. infliximab,
etanercept) are now licensed for treatment of severe RA.
TNF is a pro-inflammatory cytokine with multiple roles in the immune system.
TNF is secreted mainly by macrophages and has a number of effects on the immune system, acting
mainly in a paracrine fashion:
1) Activates macrophages and neutrophils
2) Acts as co-stimulator for T cell activation
3) Key mediator of bodies response to Gram negative septicaemia
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
4) Similar properties to IL-1
5) Anti-tumour effect (e.g. phospholipase activation)
TNF-alpha binds to both the p55 and p75 receptor. These receptors can induce apoptosis. It also
causes activation of NFkB.
Endothelial effects include increase expression of selectins and increased production of platelet
activating factor, IL-1 and prostaglandins.
TNF promotes the proliferation of fibroblasts and their production of protease and collagenase. It is
thought fragments of receptors act as binding points in serum.
Systemic effects include pyrexia, increased acute phase proteins and disordered metabolism
leading to cachexia.
Contraindications of usage of TNF- alpha antagonist:
1. Active infection
2. Active TB
3. MS (Multiple sclerosis)
4. Heart failure (NYHA grade 3-4).
5. Pregnancy
6. Breast feeding
WHAT IS THE SIGNIFICANT OF RF?
Rheumatoid factor (RF) is a circulating antibody (usually IgM) which reacts with the Fc
portion of the patients own IgG.
Rheumatoid factor is an IgM antibody with reactivity against Fc portion of IgG
RF can be detected by either:
1)Rose-Waaler test: sheep red cell agglutination –2) Latex agglutination test (less specific)
RF is positive in 70-80% of patients with rheumatoid arthritis; high titer levels are
associated with severe progressive disease (but NOT a marker of disease activity).
A positive rheumatoid factor is associated with:
More severe erosive disease
Extra-articular manifestations including subcutaneous nodules and
Increased mortality.
Other conditions associated with a positive RF include:
1. Sjogren's syndrome (around 100%)
2. Felty's syndrome (around 100%)
3. Infective endocarditis (= 50%)
4. Mixed cryoglobulinaemia (types II and III) (40 to 100%)
5. SLE (= 20-30%)
6. Systemic sclerosis (= 30%)
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
7. Polymyositis/dermatomyositis - 5 to 10%
8. General population (= 5%)
9. Rarely: TB, HBV, HIV, EBV, leprosy, syphilis, brucellosis.
In RA, RF is positive in 80% of patients, whereas in Sjogren’s syndrome and
cryoglobulinaemia, it is prevalent in up to 90% of cases.
Anti-CCP Ab (Anti-cyclic citrullinated peptide antibodies)
Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before
the development of rheumatoid arthritis.
It may therefore play a key role in the future of rheumatoid arthritis, allowing
early detection of patients suitable for aggressive anti-TNF therapy.
It has sensitivity similar to rheumatoid factor (70-80%, see below) with a much
higher specificity of 90-95%.
NICE recommends that patients with suspected RA with RF negative should be
tested for Anti-CCP Abs.
Anti-CCP antibodies are associated with rheumatoid arthritis (highly specific)
STAGES OF THE DISEASE:
1. RECENT ONSET DISEASE:
Patients meet ACR criteria for the diagnosis and classification of RA and have had evidence
of active disease for a period not more than 3 months.
2. ESTABLISHED OR PERSISTENT DISEASE:
Is characterized by active, well-defined disease for at least 6 months to 12 months .
Significant and irreversible damage may be observed at this stage, leading to functional
disability.
3. END-STAGE DISEASE:
Manifest significant destruction of previously involved joints and other affected organs but
may have little or no evidence of ongoing inflammation.
SYMTOMS AND SIGNS: ----pain ,swelling ,stiffness dominating in the morning
The RA may have a fulminant presentation or insidious course or pain with swelling and
stiffness for months or years before diagnosis.
RA may present with monoarthritis ,oligoarthritis before typical symmetrical polyarthritis.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Systemic :
Low grade fever < 38 c
Fatigue
Malaise
Chronic anemia
Elevation of ESR
Articular manifestation:
Any synovial joint may be affected
Is symmetric from one side to the
body to other.
Is symmetric within the individual
joint with the entire joint surface
area involved ex; knee , the
medial and lateral compartments are both severely narrowed in RA.
Most commonly ---MCP ,PIP ,MTP followed by wrists ,knees, elbows ,ankles , hips&
shoulders.
AIM ----early diagnosis enable for early treatment to limit the number of joints involved.
It may involve tempomandibular ,cricoarytenoid ,sternoclavicular joints.
DIP is spared and involved in osteoarthritis and psoriasis.
Patients with RA are at an increased risk of osteoporosis.
RHEUMATOID ARTHRITIS AND OSTEOPOROSIS ARE COMMON &COEXSIST.
Deformities :
1. Ulnar deviation
Ulnar deviation, also known as ulnar drift, is a hand deformity in which the swelling of the
metacarpophalangeal joints (the big knuckles at the base of the fingers) causes the fingers
to become displaced, tending towards the little finger. Its name comes from the
displacement toward the ulna . Ulnar deviation is likely to be a characteristic of
rheumatoid arthritis, more than of osteoarthritis.
2. Swan neck deformity:
The swan neck deformity is caused by joint swelling
and associated tenosynovitis with subsequent
contracture of the intrinsic (lumbrical and
interosseous) hand muscles. There is flexion at the
metacarpophalangeal, hyperextension at the
proximal interphalangeal, and flexion at the distal
interphalangeal joint evident in fingers, especially the
third, fourth, and fifth, but to a lesser extent also in
the index finger. In early disease the deformity can be passively corrected; later, functional
impairment may result from inability to flex at the proximal interphalangeal joint so that the patient
is unable to make a fist.
3. Button hole deformity
Boutonniere deformity is a deformed position of the
fingers or toes, in which (PIP) is permanently bent
toward the palm while the farthest joint (DIP) is bent
back away (PIP flexion with DIP hyperextension). It is
commonly caused by injury or by an inflammatory
condition like rheumatoid arthritis, or genetic
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
conditions like Ehlers Danlos Syndrome.
This flexion deformity of the proximal interphalangeal joint is due to interruption of the central slip
of the extensor tendon such that the lateral slips separate and the head of the proximal phalanx pops
through the gap like a finger through a button hole (thus the name, from French boutonnière "button
hole"). The distal joint is subsequently drawn into hyperextension because the two peripheral slips of
the extensor tendon are stretched by the head of the proximal phalanx (note that the two peripheral
slips are inserted into the distal phalanx, while the proximal slip is inserted into the middle phalanx).
This deformity makes it difficult or impossible to extend the proximal interphalangeal joint.
4. Tendon rupture
Rupture of the extensors of the fourth and fifth digits is caused by active synovitis and invasive
synovial proliferation. Wrist instability with prominence of the eroded ulnar styloid process can also
shear the ulnar tendons.
If the clinical disease remains active ,hand function will slowly deteriorate.
The wrists ---radial deviation ,volar subluxation ,carpel tunnel
syndrome
The feet ((MTP))
Involved early in almost all cases
Are secondary only to hand involvement in problems
Subluxation of the toes at MTP is common and leads to the dual problem of
skin ulceration on the top of toes and painful ambulation.
Synovial cyst:
A Baker's cyst((popliteal cyst)) is a benign swelling of the semimembranosus or more rarely some other
synovial bursa found behind the knee joint. (( William Morrant Baker (1838–1896) )). This is not a "true" cyst,
as an open communication with the synovial sac is often
maintained.
Baker's cysts arise between the tendons of the medial head of
the gastrocnemius and the semimembranosus muscles. They
are posterior to the medial femoral condyle.
The knee produces excess synovial fluid that may accumulate
in the poplitael space.
The synovial sac of the knee joint can, under certain
circumstances, produce a posterior bulge, into the popliteal
space. When this bulge becomes large enough, it becomes
palpable and cystic. Most Baker's cysts maintain this direct
communication with the synovial cavity of the knee, but sometimes, the
new cyst pinches off. A Baker's cyst can rupture and produce acute pain
behind the knee and in the calf and swelling of the calf musclesThe cyst
may cause problems by:
A. Pressing on the popliteal nerve ,artery and vein
B. Rupture
C. May dissect into the tissues of the calf
Dissections may produce only minor symptoms ,feeling of
fullness.
Rupture of the cyst with extravasation of the inflammatory content produce significant pain and
swelling which may be confused with thrombophlebitis or DVT.
Diagnosis:
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
1. CLINICALLY: Diagnosis is by examination. A Baker's cyst is easier to see from behind with
the patient standing with knees fully extended.
It is most easily palpated (felt) with the knee
partially flexed.
2. DOPPLER USS: Diagnosis is confirmed by
ultrasonography, although if needed and there is
no suspicion of a popliteal artery aneurysm then
aspiration of synovial fluid from the cyst may be
undertaken with care.
3. MRI: An MRI image can reveal presence of a
Baker's cyst.
Baker's cyst on axial MRI with communicating channel
between the semimebranosus muscle and the medial head
of the gastrocnemius muscle.
An infrequent but potentially life-threatening complication is
a deep vein thrombosis (DVT). Quick assessment of the
possibility of DVT may be required where a Baker's cyst has
compressed vascular structures, causing leg edema, as this
sets up conditions for a DVT to develop.
A burst cyst
commonly causes
calf pain, swelling
and redness that
may mimic
thrombophlebitis.
Treatment -----
intra-articular
glucocorticoids
1. Baker's cysts usually require no treatment unless they are symptomatic.
2. Initial treatment should be directed at correcting the source of the increased fluid production.
3. Often rest and leg elevation are all that is needed.
4. If necessary, the cyst can be aspirated to reduce its size, then injected with a corticosteroid to reduce
inflammation.
5. Surgical excision is reserved for cysts that cause a great amount of discomfort to the patient.
6. A ruptured cyst is treated with rest, leg elevation, and injection of a corticosteroid into the knee.
7. Recently, prolotherapy has shown encouraging results as an effective way to treat Baker's cysts and
other types of musculoskeletal conditions.
8. Cryotherapy
Ice pack therapy may sometimes be effective way of controlling the pain caused by Baker's cys
The spine ----most of the spine is spared except C1 C2 articulation.
RA have cervical spine involvement between 11% and 58% of these patients having neurological involvement.
Many of these patients have cervical myelopathy.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Whatever the underlying disease process, the compression is usually progressive and will often require surgical
intervention to prevent further disability. Many patients experience significant improvement in symptoms
after surgery, so operative intervention should be considered for almost all patients.
Epidemiology
Cervical myelopathy is more common in men and tends to present earlier than in women. Changes
are more common in patients with RA where 85% of those with moderate to severe disease will
have x-ray changes Bony ,erosions and ligament rupture .
Subluxation is the end result.
The underlying cause of the condition is compression of the long tracts in the spinal cord. The
normal diameter of the cervical spinal canal is between 17 mm and 18 mm. When this diameter
falls below 12 mm to 14 mm for any reason this is likely to cause stenosis and myelopathic
symptoms. The average diameter of the spinal cord in the cervical spine is 10 mm.
Symptoms:
Patients may present with a range of symptoms and many of these are non-specific. It is important to
remember that although cervical myelopathy is a disease of the cervical spine it may manifest with
lower as well as upper limb symptoms.
The classical presentation is loss of balance with poor coordination, decreased dexterity, weakness,
numbness and in severe cases paralysis. Pain is a symptom in many patients but it is important to
remember that it may be absent which often leads to a delay in diagnosis. In older patients it often
manifests with a rapid deterioration of gait and hand function.
Common presenting complains are:
heavy feeling in the legs
poor exercise tolerance
radiculopathy
poor fine motor skills
L’Hermitte’s phenomenon - intermittent electric shock sensations in the limbs,
exacerbated by neck flexion
numbness and tingling in the limbs
Late in the disease where compression is severe, if surgical decompression is not
performed the symptoms progress to sphincter dysfunction and quadriparesis. CSM is the
most common cause of acquired spastic paraparesis in adults.
Examination findings
Patients present with a number of clinical findings which are predominantly upper motor neuron
signs.
Weakness is more severe in the upper limbs.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Ataxic broad based gait.
Hypertonia .
Hyperreflexia .
Ankle clonus - (more than three beats is considered pathological).
Babinski sign .
Hoffman’s reflex - flicking of the terminal phalynx of the middle or ring finger
causing concurrent flexion at the terminal phalynx of the thumb and index finger.
Finger escape sign - the small finger spontaneously abducts due to weak intrinsic
muscles.
DIAGNOSIS:
Where instability is suspected to be the cause of symptoms (especially in RA) flexion and
extension views of the cervical spine will show abnormal motion
Advice ------ TO AVOID NECK FLEXSION
Atlanto axial subluxation
Cervical dislocation
Spinal cord copmression
The cricoarytenoid ----responsible for adduction and abduction of vocal cords.
If involved , it manifest as feeling of fullness in throat ,hoarsness ,stridor ,acute respiratory
stress
The extra articular manifestation:
More common in patients with positive rheumatoid factor.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
1. Subcutaneous nodules:
o Seen in 25% of RA with positive RF
o Patient with nodules but negative RF should be
carefully evaluated for an alternative diagnosis ---
((GOUT))
o May occur anywhere ----lungs ,heart ,eyes
o Occur most commonly subcutaneous on extensor
surface ,over joints or pressure joints ,sacrum
,occipit.
o Non tender ---unless traumatized
o Firm ,have a characterized histologic picture
,triggered by
small vessel
vasculitis.
o A
syndrome of increased nodulosis
((despite good control of the
disease )) has been described with
methotrexate.
o Have a central area of
fibrinoid necrosis surrounded by a
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
zone of palisades of elongated histocytes and peripheral layer of
connective tissue
2. Vasculitis :
Rheumatoid Vasculitis (RV) is an
unusual complication of longstanding,
severe rheumatoid arthritis. The active
vasculitis associated with rheumatoid
disease occurs in about 1% of this
patient population.
RV is a manifestation of “extra-
articular” rheumatoid arthritis and
involves the small and medium-sized
arteries in the body. In many of its
disease features, RV resembles
polyarteritis nodosa.
Symptoms depend on which
arteries are involved and which organ
they supply blood to.
For instance, if there is vasculitis of
arteries that supply the skin, then
symptoms will vary with the area of skin
to which the affected artery supplies
blood. If say the artery supplies blood to
the fingertips and nails, then the area
around the tips of fingers and nails may
become red and swollen. If larger arteries
and veins are involved, then painful red
rashes may appear on the hands and legs.
Excessive inflammation may lead to
formation of ulcers, and managing them
can be an uphill task.
If vasculitis involves the nerves, there may
be a loss of sensation leading to
weakness and a tingling sensation in hands and feet.
Vasculitis that affects larger arteries can lead to complete blockage of blood supply to
hands and feet, causing gangrene of the toes and fingers. The worst cases could display
stomach pain, cough, chest pain, heart attack, stroke etc.
Systemic vasculitis, which spreads to multiple organs from the original site usually also,
shows up as fever, loss of appetite, loss of energy and weight loss.
a) Digital infarcts
b) Leucocytoclastic vasculitis --- palpable purpura --if present DMARDS is
adviced.
c) Pyoderma gangrenosum
The ulcer is extensive and threatens the underlying bone.
3. CVS:
Uncommon
Increased mortality & mobidity from CAD.
Risk factors --- sedentary life ,medications , chronic inflammations
Pericardial effusion
Common
Detected in 50% of patients by ECHO.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Asymptomatic
Can cause constrictive pericarditis
Heart block by rheumatoid nodules.
PERICARDITIS
Pain 1% .can lead to temponade ,constriction((in 30%))
NODULES
Causes conduction abnormalities and valvular
CORONARY ARTERITIS
Causes IHD ((RA carries a similar risk to T2DM)) ,MI , CCF
MYOCARDITIS
Rheumatoid arthritis: patients have an increased risk of IHD
4. Respiratory system: ((pleura, airways ,parenchyma))
1) Pleural effusion :
More commonly in male ,small and asymptomatic
Characterized by cellular exudates ,high protein,cholestrol &LDH ,low glucose&PH
D/D Empyema
2) Rheumatoid nodules:
May occur in the lung , usually subpleural especially in men.
It is usually solid ,single or multiple which may calcify ,cavitate or become infected.
An aggressive diagnostic work up should be performed when rheumatoid nodules are
detected.
3) Diffuse interstitial fibrosis & bronchiectasis :
52 year old man with seropositive rheumatoid arthritis who presented with dyspnea
and hypoxemia. AP chest x-ray showed increased interstitial markings with volume
loss and tracheal deviation. CT scan showed honeycombing and traction bronchiectasis
consistent with interstitial lung disease associated with rheumatoid arthritis.
Typical finding ---Dyspnea with honeycombing((peripheral& central changes)).
Symptomatic and aggressive in < 10%
4) BOOP:
Carry poor prognosis
May occur with D penicillamine or gold therapy
Patient have dyspnea ,hyperinflated chest x ray and small airways obstruction on PFT.
5) Methotrexate pneumonitis (it is potentially life-threatening and occurs in 1-5%
of patients who are treated with methotrexate)
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
6) Pleurisy
7) Pneumonia
8) Bronchitis ,amyloidosis ,pleural thickening
9) Caplan’s syndrome (RA + massive fibrotic nodules with pneumoconiosis
occupational coal dust exposure).
10) EYE: (it is common and occur in 25% of patients)
1. keratoconjunctivitis sicca (most
common): (dry, burning and gritty eyes
caused by decreased tear production)
2. Episcleritis (erythema only)
Scleritis (erythema and pain)
Corneal ulceration (Corneal melts =
perforated corneal ulceration).
3. Keratitis
4. Steroid-induced cataracts
5. Chloroquine retinopathy
6. Scleromalacia performans ---perfoartion of orbit
Rheumatoid nodules involving the sclera of the eye may result in scleromalacia. The
bluish choroid is visible because of thinning of the sclera. The
surrounding bulbar conjunctiva appears slightly atrophic, and
superficial vessels are dilated. Focal chronic inflammatory
cell infiltration and necrosis may appear in the sclera. When
these changes become more extensive, the lesion resembles
the subcutaneous nodule of rheumatoid arthritis
Bluish discoloration ---thining of the sclear
7. Xerostomia
8. Parotid gland sweeling
9. Lymphadenopathy
Episcleritis is not painful, Scleritis is painful
11) Osteoporosis
12) Increased risk of infections (possibly atypical): CMV-associated colitis.
13) Depression
14) CNS:
Paraesthesia in hands that may let him awake from sleep
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Peripheral nerve entrapment syndromes ---carpel & tarsal tunnel syndrome
Mononeuritis multiplex secondary to vasculitis
Myelopathy due to subluxation of C1 C2
15) Amyloidosis >>> Renal failure (Nephrotic range proteinuria) >>> high levels of
serum amyloid A protein which is also an acute phase reactant, the kidneys are
usually normal size, or slightly large and hepatomegaly.
16) AIHA (autoimmune haemolytic anaemia): warm type, +ve DGT (direct globulin
test) (Coomb’s test), spherocytosis, ↑RTX & ↑ LDH.
17) FELTY SYNDROME—1%:
RA + splenomegally + neutropenia
It is usually occurs in patients with long-standing seropositive RA.
Two third of the patients are female (60-70% female predominance).
It is usually recognised from the 5th decade onwards in patients who have
had RA for an average of 10 years or more.
It may be accompanied by hepatomegally ,thrombocytopenia
,lymphadenopathy and fever.
C/P: Active RA + Leukopenia + Lymphadenopathy + Splenomegaly + also leg
ulcers, recurrent infections (URTI) and Episcleritis may be present.
ANA is positive in more than 90% of patients with Felty’s syndrome.
No specific treatment
Splenctomy may be indicated if sever neutropenia exsists < 500 cells/ml with
chronic non healing leg ulcers or recurrent bacterial infections.
Seen in 1% of RA with RF positive .subcutaneous nodules
95% of patients are HLA DR4 with positive RF.
The leukopenia is generally neutropenia (( < 2000/mm3))
Active RA on methotrexate with leukopenia >>>? Methotrexate-induced or Felty’s syndrome (+ve ANA).
Complications:
Bacterial infections ((20 fold increase))
Chronic non healing leg ulcers
Non hodgkins lymphoma (( 13 fold increase))
Nodular regenerating hyperplasia of the liver with portal HTN & varices.
Sever bacterial infections correlate with neutrophil count of < 1000/mm3
2002--- Now days ,splenectomy & lithium are out of favour.
G-CSF---has been used & shown effective at increasing WBC count &
decreasing in some patients.
Dose Neupogen 2—5 micg/kg/day to patient with RA + recurrent infections
until neutrophils > 1500 /mm3 THEN weekly for maintenance.
G-CSF –can increase arthritis and vasculitis when WBC count is raised.
LGL syndrome---large granular lymphocyte
Have a natural killer and antibody dependent cell mediated cytotoxicity
activity ,bearing CD2 ,CD3 ,CD8 ,CD16 ,CD53 surface phenotypes on PBF.
A few RA patients have WBC counts dominated by large granular lymphocytes
and have almost complete absence of neutrophils
Thought to be a variant of T cell leukemia.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
When seen in patient with RA ,these patients have a good prognosis with
neutropenia often responding dramiatically to methotrexate.
D/D:
Viral syndromes----HBV ,HCV ,EBV ,parvovirus
Prsoriatic arthritis
Reactive arthritis
Tophaceous gout
SLE
Sarcoidosis
Lyme disease
Osteoarthritis
Rheumatic fever
Polymylgia rheumatic
Calcium pyrophosphate DISEASE
D/D of subcutaneous nodule and arthritis:
1. Rheumatoid arthritis
2. Rheumatic fever
3. Gout
4. Sarcoidosis
5. Xanthoma
PHYSICAL EXAMINATION:
At intervals not more than 6 months.
Examination to assess changes in previously inflamed joints or appearance of inflammation
in an uninvolved joints.
If the hands but not the feet are involved, a 28 joint examination is appropriate: wrist,
elbows, shoulders, knees, MCP’S, PIP’S of hands.
If the feet but not the hands are involved: MTP; PIP, of feet can be assessed instead of
hand joints.
The joints should be evaluated for the presence of: swelling, tenderness, loss of motion
and deformity.
In addition ,examination for extra-articular manifestations is mandatory.
HOW TO PREDICT PATIENTS WITH SEVER DISEASE AND POOR PROGNOSIS ?
1. Female sex.
2. Insidious onset
3. Generalized polyarthritis ---small &large >20
4. Extra articular disease ----nodules and vasculitis
5. Poor functional status at presentation
6. Persistently elevated CRP or ESR
7. Rheumatoid factor positive – RF+ve
8. Anti-CCP antibodies
9. HLA DR4
10. X-ray: early articular erosions (e.g. within the first 6 months of
presentation and in less than < 2 years).
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
AMERICAN COLLEGE OF RHEUMATOLOGY CRITERIA FOR RA :
Morning stiffness
Arthritis of three joint areas > 6 weeks
Arthritis of the hands
Systemic arthritis
Rheumatoid nodules
Serum rheumatoid factor
Radiologic changes:
Erosions of periarticular bone
Cartilage destruction
Loss of joint space
Laboratory investigation:
Acute phase reactants: CRP, ESR.
N-N anemia.
Hypo-albuminemia.
Thrombocytosis.
RF titer ?
Anti-CCP Ab titer
imaging techniques:
Baseline x-ray of hands and feet.
Repeated 6-12 monthly.
CT scan, USS, MRI are more sensitive.
CBP---anemia :
Seen in the majority of patients
Proportional to the activity of disease
Therapy that controls the disease will result in normalization of HB
Thrombocytopenia is common.
Acute phase reactants:
ESR and CRP parallel the activity of disease
Persistent elevation carry poor prognosis with joint destruction and
mortality
WBC: increased /decreased
DIAGNOSIS:
There is no single finding on physical examination or laboratory testing that is
pathognomic for RA.
NICE have stated that clinical diagnosis is more important than criteria such as
those defined by the American College of Rheumatology.
The most commonly used classification criteria are the American College of
Rheumatology criteria. These criteria do not perform well in early disease.
The criteria for diagnosis :
A) Not designed specifically for diagnosis ,used as diagnostic aid.
B) The first five criteria are all clinical ,met by physical examination /talking
to the patient.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
C) The first four criteria need to be present for at least 6 weeks before
diagnosis of RA can be made. WHY?
Many viral related syndromes often cause self limited polyarthritis that
looks identical to RA but usually lasts 2—3 weeks .
This leads to delay of diagnosis and therapy of RA.
Rheumatoid arthritis is a clinical diagnosis.
The diagnosis reguires the presence of inflammation.
The classic features are:
Symmetrical inflammatory polyarthritis
Arthritis affecting the small joints of the hands and feet.
Diagnostic tests are:
1) RF: there are many false positive and negatives.
2) Anti CCP antibody: more specific for rheumatoid arthritis.
3) ANA: present in 20-30% of patients with rheumatoid arthritis.
Target population. Patients who
1) Have at least 1 joint with definite clinical synovitis
2) With the synovitis it is not better explained by another disease
Classification criteria for rheumatoid arthritis (add score of categories A-D; a
score of 6/10 is needed definite rheumatoid arthritis)
Aletaha et al. 2010 Rheumatoid arthritis classification criteria: an American
College of Rheumatology / European League Against Rheumatism
collaborative initiative
A. Joint involvement 1 large joint 0
2 - 10 large joints 1
1 - 3 small joints (with or without
involvement of large joints)
2
4 - 10 small joints (with or without
involvement of large joints)
3
10 joints (at least 1 small joint) 5
B. Serology (at least 1 test result is
needed for classification)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
C. Acute-phase reactants (at least 1
test result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP and abnormal ESR 1
D. Duration of symptoms < 6 weeks 0
> 6 weeks 1
WHAT ARE THE X RAY CHANGES?
Early x-ray findings:
soft-tissue swelling
loss of joint space
Periarticular (juxta-articular) osteopenia and
osteoporosis
Periarticular decalcification
Late x-ray findings:
o Periarticular erosions
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
o Subluxation
In the early stages of an insidious onset of the RA
disease, the acute phase markers CRP and ESR are
often normal, particularly when small joints are
involved.
o At this stage of early RA , the diagnostically most
informative test is hand and feet X-ray which
shows periarticular osteopenia and marginal
erosions at affected joints.
o Foot joints are often radiologically affected
beforehand joints
Periarticular osteopenia and osteoporosis would point towards a diagnosis
of (RA).
Loss of joint space is common in both RA and OA also in Pseudogout
1- mild disease:
Arthralgia.
At least 3 inflamed/swollen joints.
No extra-articular disease.
Negative or positive RF and/or anti-CCP Ab.
High ESR or serum C-RP.
NO evidence of erosions or cartilage loss on plain radiographs.
2-Moderate disease:
6-20 inflamed joints.
No extra-articular disease.
High ESR and C-RP.
Positive RF and/or anti-CCP Ab.
Evidence of inflammation on plain radiographs: osteopenia, peri-articular swelling,
minimal joint space narrowing and small peripheral erosions.
3- Severe disease:
>20 Persistently inflamed joints, or rapid decline in functional capacity.
High ESR, C-RP.
Anemia of chronic disease.
Hypo-albuminemia.
Positive RF( often high titer) and/or anti-CCP Ab.
Extra-articular disease.
Plain radiographs demonstrating rapid progression of bony erosions and loss of cartilage
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
TREATMENT:
There is no cure for RA.
It is a lifelong disease process that requires lifelong therapies.
The patient-physician interaction is mandatory.
For care of RA patients ,we need :
1. Primary care physicians
2. Rheumatologist
3. Physical therapist
4. Occupational therapist
5. Orthopedic surgeons
The goal of therapy for RA is :
A) To put the disease in remission
B) To maintain the remission
Non-pharmacological and preventive treatment
1-Pateints education and counseling:
About the disease.
Remove miss-concepts.
Treatment strategies and plan.
2-REST.
3-EXERCISES:
Exercises to increase muscle strength (isometric, isotonic and iso-kinetic)
Aerobic exercises: walking, swimming and cycling.
4-PHYSICAL THERAPY:
Application of heat and cold.
Rest and rest splinting.
Passive and active exercises.
Relaxation techniques.
4- OCCUPATIONAL THERAPY:
Education regarding joint protection and self-care.
Assistive devices and splints.
5-NUTRITION AND DIATRY THERAPY:
Anorexia should be treated.
Diet rich in fish oil.
Decrease body weight.
6-BONE PROTECTION:
Bone loss due to: disease, immobility, use of GC.
Limit use of GC to < 6 months and doses <7.5 mg/day.
Elemental calcium 1000-1500 mg /day and 400-800 IU of vitamin D /day.
Consider anti-resorptive therapy with a bisphosphonate.
7-MODIFYING RISK FACTORS FOR ATHEROSCLEROSIS:
Increased risk of CAD associated mortality and morbidity.
Modify risk factors: cigarette smoking, hyper-lipidemia, HTN, sedentary life style.
Consider HMG-COA reductase inhibitors.
8-VACCINATIONS:
Patients receiving immuno-suppressive drugs should not receive live vaccines.
If otherwise indicated use killed viruses or poly-saccharide vaccines.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Patients with evidence of joint inflammation should start a combination of disease
modifying drugs (DMARD) as soon as possible.
Other important treatment options include analgesia, physiotherapy and surgery.
Initial therapy:
In NICE guidelines it is recommend that patients with newly diagnosed active RA
start a combination of DMARDs (including methotrexate and at least one other
DMARD, plus short-term glucocorticoids) (EX: Methotrexate + sulfasalazine +
short-course of prednisolone as bridging therapy).
DMARDs:
a. Methotrexate is the most widely used DMARD.
b. Sulfasalazine (500 mg tab)
c. Leflunomide (Arava® 20 mg tab)
d. Hydroxychloroquine (HCQ) (plaquenil® 200 mg tab): less effective.
1. NSAIDS:
Important for symptomatic relief
They play a minor role in altering the disease process
Many clinicians waste valuable time switching from one NSAIDS to another before starting DMARD
therapy.
COX 2 agents are used more widely with small doses of aspirin.
Two types of COX:
COX-1: constitutional, vasodilatation, increase PG synthesis, and inhibit PLT aggregation.
COX-2: inducible , increases pro-inflammatory cytokines
Arachidonic acid ------COX--------PG
Selective COX-2 inhibitors have less side effects
Celecoxibe ,Etoricoxib.
COX-1 COX-2
Indomethacine
aspirin
piroxicam
ibuprofen
diclofenac
meloxicam
celecoxib.
Side effects:
GIT: 1% OF RA patients are admitted each year
with amajor GIT bleeding
Endoscopic evidence of ulcer is found in 20% even
in absence of symptoms
Prevalence of PUD is 14-31%.
Risk factors:
2) Age > 60 years 1) Type of NSAID’S
3) Multiple NSAID’S 7) Dose
4) Corticosteroid use 8) Smoking
5) Anti-coagulant use 9)H/O PUD
6) Alcohol 10)Co-morbidity
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
To reduce the incidence of GIT side effects:
A. Use selective COX-2 inhibitors
B. Use of PG analogues: misopristol---40% reduction of GIT toxicity
Other SE of NSAID’S:
a. Renal: ARF, analgesic nephropathy, papillary necrosis, nephritic syndrome.
b. Aseptic meningitis
c. Sodium and fluid retention.
1. GLUCOCORTICOIDS:
RA was chosen as first disease to test this new therapy in 1948
AIM--For symptomatic improvement and significant decreased of the radiological progression.
It Remains the most potent anti-inflammatory treatments available because of rapid onset of action.
They are ideally suited to help control the inflammation of RA while the much slower acting DMARDS
are starting to work.
The guidelines of GC are:
a) Prednisolone > 10gm rarely indicated for articular diseases
b) Avoid using GC without DMARDS
c) Use GC as bridge therapy to affective DMARD .
This is to shut off inflammation rapidly with GC and to taper them as DMARD is kicking in.
d) Minimized dose and duration ---taper to the lowest dose that controls arthritis
e) Consider prophylaxis (( Bisphosphonate )) for osteoporosis.
2. DMARD:
GENERAL FEATURS:
1- They do not have anti-inflammatory effect, but they alter the course of the disease over a
period of months. These medication take 2—6 months to reach maximum effect
2- If started early in the course of the disease , they will delay or prevent radiographic
progression. ((the gold standard of halting or slowing the radiographic progression of RA)).
3-They induce symptomatic remission in 40-60% of patients.
4.They Have been shown to be effective in treating both early & more advanced RA.
a. Methotrexate is the most widely used DMARD.
b. Sulfasalazine (500 mg tab)
c. Leflunomide (Arava® 20 mg tab)
d. Hydroxychloroquine (HCQ) (plaquenil® 200 mg tab): less effective.
Methotrexate is an antimetabolite which inhibits dihydrofolate reductase (DHFR enz), an enzyme essential
for the synthesis of purines and pyrimidines.
Is a structural analogue of folic acid.
FH2-------DHFR---------FH4
In RA; increases extra-cellular adenosine, inhibit methylation reactions, suppression of IL-1
beta production.
Pharmacology: oral, IM, SC routes
80-90% excreted un-changed by the kidney
50% bound to plasma protein
Dose: 7.5 mg/week , increased gradually to 25mg/week
Side effects:
1. Common SE: nausea, abdominal Pain, loose stool, stomatitis, macular punctate rash,
alopecia, fever , headache, fatigue , inability to concentrate , macrocytic anemia.
2. Hepatotoxicity: liver fibrosis:
Base line AST, ALT , S.albumin, S.bilirubin, PT, HBsAg, HCV. Then every 4-8 weeks.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
3. Liver biopsy should be performed if 6 of 12 tests are abnormal in any year.
4. Interstitial lung disease: 3-5% acute-chronic, occurs within the first 2 years of therapy
5. Nodulosis
6. Lymphoproleferative malignancies
7. Terratogenic
8. Osteoporosis
9. Addition of folic acid or folonic acid reduces MTX SE EXCEPT lung and liver toxicities
Adverse effects:
1) Hepatitis and Liver cirrhosis
2) Myelosuppression
3) Pneumonitis
4) Pulmonary fibrosis
5) Mucositis
FBC, U&E and LFTs need to be regularly monitored.
Folic acid 5mg once daily should be co-prescribed, taken more than 24 hours after methotrexate
dose. Only one strength of methotrexate tablet should be prescribed (usually 2.5 mg).
Avoid prescribing trimethoprim or cotrimoxazole concurrently - increases risk of marrow aplasia.
NB: Methotrexate is a folic acid antagonist which can result in multi-organ
failure in overdose.
Folinic acid (Calcium folinate) (Leucovorin) IVI is the antidote for the effect of
methotrexate on the haematopeic system and should be given IV infusion as
soon as possible, regardless of the liver function tests
Dose: 75 mg in the first 12 hrs, and can then be followed by 6-12 mg every 4
hrs.
Blood transfusion may be required in exceptional circumstances.
Supportive measures by good hydration and urinary alkalinization may be
used.
Standard dialysis is ineffective in removing methotrexate, although
intermittent high flux dialysis may be of value.
Complications to be in mind due to methotrexate:
An MCV greater than 105 fL warrants checking B12, folate and TSH and treating any abnormality.
Liver function tests should be checked 3 monthly.
Urea, C. and electrolytes should be checked 6 monthly (( eGFR < 50 mL/minute –stop methotrexate)
In addition to this monitoring, any clinical signs of toxicity should be monitored for. If the patient
develops rash, oral ulceration, sore throat, easy bruising or bleeding, shortness of breath,
abdominal pain, nausea, vomiting, diarrhoea or jaundice, methotrexate should be withheld until
discussed with the specialist team.
In the setting of acute infection, most DMARDs (except hydroxychloroquine) should be
discontinued until the infectious process has resolved.
IF patient on methotrexate and develop lower respiratory tract infection with normal
CXR, CBC, LFTs, U&E.
The most appropriate action is to Stop methotrexate temporarily + Antibiotics (oral/IV).
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Methotrexate-related lung toxicity:
A large spectrum of diseases ranging from interstitial pneumonitis to cough, pleuritic chest pain
and SOB related to lung infiltration, associated with bilateral pleural effusions.
TTT: Methotrexate withdrawal and replace with anti-TNF or anti-CD20 antibody.
Sulfasalazine
PHARMACOLOGY:
3O% absorbed rapidly by small intestine and then returned via entero-hepatic circulation
into bile unaltered.
90% of the ingested drug reaches the large intestine as an intact molecule.
In the colon sulfasalazine is reduced by action of bacterial enzyme……Azoreductase to
sulfapyridine and 5-ASA.
All sulfapyridine is absorbed and 5-ASA is largely excreted in feces.
Sulfapyridine is subsequently metabolized in liver via hydroxylation and acetylation.
The half-life of the drug is prolonged in slow acetylators.
MECHANISMS OF ACTION:
Sulfapyridine is the active moiety in RA.
Mechanism of action is uncertain in RA.
Inhibition of a nuclear factor kappa B …….decrease in inflammatory cytokines.
Inhibition of TNF-a expression via apoptosis of macrophages.
Adverse effects:
Idiosyncratic: skin reaction ,hepatitis,pneumonitis, agranulocytosis, aplastic anemia
Dose-related: GIT, CNS, leukopenia, megaloblastic anemia
Oligospermia
Dose:500mg/day increased by 500mg per week until 2-3 g/day.
Lab. Monitoring: CBC and LFT at initiation of therapy then every 2 weeks in the first 3
months and then monthly in the second 3m, then every 3 m ,6 months after a year .
Sulphasalazine should be withheld until discussion with the specialist team if:
1. The white cell count is less than 3.5
2. Neutrophils is less than 2, or
3. Platelets are less than 150.
ANTI-MALARIAL DRUGS
Chloroquine-hydroxychloroquine---4-aminoquinolones
Quinacrine---------9-aminoacridine cpd
Pharmacokinetics
70% absorbed, Wide tissue distribution
Chloroquine decreases bioavailability of MTX.
Cimetidine decrease chloroquine clearance by 50%
Cigarette smoking increases metabolism of antimalarial drugs.
Actions:
Changes the acid milieu of the cell---lysosomotropic effect
Decreseas lymphcyte proliferation.
Decreases TNF-ALPHA.
HC has a mild anti-coagulant effect.
Adverse effects:
1-GIT: nausea, vomiting , diarrhea, rarely hepatotoxicity.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
2-Skin changes: skin rash occurs in 10% of patients with HC and chloroquine.
Hyperpigmentation of skin hypopigmentation of hair.
Quinacrine causes yellowish discoloration of skin.
3-Ophthalmologic disease:
Corneal deposit
Retinopathy: permanent vision loss occurs in 3-4% of patients on HC, and in 10% of
chloroquine
Eye check up every 6-12 months.
4-CNS: headache , dizziness, tinnitus. insomnia.
5- neuromuscular and cardiac: neuromyopathy , cardiomyopathy.
6- agranulocytosis, aplastic anemia.
Anti-malarials are usually given to patients with mild to moderate disease, and may be
combined with NSAIDS or other DMARDS including MTX with or without sulfasalazine.
They improves functional status, although they may not slow joint erosions.
Hydroxychloroquine Hydroxychloroquine ocular toxicity includes:
1)Keratopathy 2) Ciliary body involvement 3) Lens opacities (Lenticular deposits)
4) Retinopathy.
Retinopathy is the major concern; the others are more common but benign.
The incidence of true hydroxychloroquine retinopathy is exceedingly low.
Risk factors include:
1. Daily dosage of hydroxychloroquine
2. Cumulative dosage
3. Duration of treatment
4. Coexisting renal or liver disease
5. Patient age, and
6. Concomitant retinal disease.
Patients usually complain of difficulty in reading, decreased vision, missing central vision, glare,
blurred vision, light flashes, and metamorphopsia. They can also be asymptomatic.
Leflunomide (Arava® 20 mg tab)
Is an isoxazole derivative approved by FDA for treatment of RA.
Orally administered and has a long half-life (15 hours).
Current place of use in RA probably occupies a niche between MTX and biologic agents
It is a prodrug and under goes extensive entero-hepatic circulation.
Converted into the active metabolite MALANONITRILAMIDE (A77-1726).
MODE OF ACTION:
i. It inhibit enzyme DIHYDRO-ORATATE-DEHYDROGENASE…important for pyrimidine
(rUMP) synthesis.
ii. Activated T- lymphocytes needs 8 fold increase in (r UMP) to move from G1 phase
to S phase of cell cycle
iii. It blocks TNF-mediated NF-KAPPA B activation
iv. Inhibits induction of nitric oxide synthetase
v. Decrease production of PGE2 and IL-6 and matrix metalloproteinase.
vi. Inhibits osteoclastogenesis.
DOSE:
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
100mg/day for 3 days, followed by 20 mg/day.
ADVERSE EFFECTS:
1- most common: nausea, diarrhea, skin rash, alopecia, respiratory tract infections.
2-hepatotoxicity
3-? Interstitial pneumonitis.
4- HTN.
5- Weight loss. > 10%-----weather decrease the dose or stop it
6-neuropathy.
Generally, most hepatic events occur within the first 6 months of use. It is recommended liver
function tests (LFTs) be checked monthly for 6 months and, if stable, 2 monthly thereafter.
If AST or ALT is between 2 and 3 times the upper limit of normal, and the leflunomide dose is more
than 10 mg daily, the dose should be reduced to 10 mg and LFTs rechecked weekly until normalised.
Azathioprine (Imuran)
Azathioprine is metabolised to the active compound mercaptopurine, a purine analogue that
inhibits purine synthesis (inhibits DNA synthesis). A thiopurine methyltransferase (TPMT) test may
be needed to look for individuals prone to azathioprine toxicity.
Azathioprine - check thiopurine methyltransferase deficiency (TPMT) before treatment
Thiopurine methyltransferase (TPMT) deficiency is present in about 1 in 300 people and
predisposes to azathioprine related pancytopenia.
The enzyme activity of TPMT is under the control of a genetic polymorphism. 90% of the population
have normal or high enzyme activity, that is, are homozygous for the wild-type allele. 10% of the
population have intermediate levels of TPMT activity, that is, one wildtype and one variant allele.
One in 300 people have no functional enzyme activity.
Adverse effects include:
1) Bone marrow depression >>> Pancytopenia
2) Hepatotoxicity
3) Pancreatitis
4) Nausea/vomiting
A significant interaction may occur with allopurinol and hence lower doses of azathioprine should
be used (so you may give only 25% of the usual dose of azathioprine).HOW?
The prodrug azathioprine is metabolised to its active compound 6-mercaptopurine (6-MP).
6-MP undergoes catabolic oxidation to 6-thiouric acid by xanthine oxidase.
Allopurinol has a peak onset of action of one to two weeks and works by inhibiting
xanthine oxidase.
Co-administration of these drugs (Imuran + Allopurinol) may lead to accumulation of 6-MP
(6-MP toxicity) and increases the risk of myelosuppression (aplastic anaemia).
The newer xanthine oxidase inhibitor, Febuxostat, can also result in the same problem and
is also contraindicated.
Febuxostat is a non-purine, selective xanthine oxidase inhibitor unlike allopurinol, which is
a purine analogue inhibitor of xanthine oxidase.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Anti-cytokine therapy in RA --TNF-inhibitors (Biologic therapy):
THE CONCEPT:
T-CELL SUBSETS:
Th1 cells:
Act as inflammatory cells.
Induce cell-mediated response, which predominate in : RA, acute allograft rejection, GVH
disease, psoriasis, PSA.
Secrete the following pro-inflammatory cytokines:
1. IL-2
2. IFNg
3. TNF-a
4. IL-15
5. IL-18
Th2 cells:
A. Stimulate Ab production by B cells.
B. Augment eosinophil response.
C. Stimulation of Th2 cells is associated with chronic GVH disease, SLE, PSS
D. Th2 cells secrete the following cytokines:
1. IL-4
2. IL-5.
3. IL-9.
4. IL-10.
5. IL-13.
Down-regulation of pro-inflammatory cytokines
IL-1b and TNF-a are considered to be the major pro-inflammatory cytokines
involved in the pathogenesis of RA and chronic inflammatory diseases.
Secreted by synovial macrophages…proliferation of synovial cells and increase
synthesis of collagenase….degrading cartilage, bone resorption and inhibit
proteoglycan synthesis.
IL-1b and TNF-a also induce the expression of cellular adhesion
molecule……inflammatory cell recruitment……release more cytokines.
To down-regulate or inhibit the effector function of these cytokines in vivo:
4 general approaches have been used:
1-Cell surface receptor antagonist.
2-Soluble receptor antagonist.
3-Anti-bodies.
4-Anti-sense oligodeoxynucleotides
Up-regulation of inhibitory cytokines
IL-10, IL-4 suppress Th1 responses.
IL-10 up-regulates IL-1ra
The current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs
including methotrexate
Adverse effects of TNF blockers include reactivation of latent tuberculosis and demyelination.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
The risk of TB reactivation is most pronounced in the first 3 months of treatment.
The current British Thoracic Society BTS guidelines therefore recommend a clinical examination,
chest radiograph and thorough history taken to check for prior TB.
In the UK, patients have a baseline CXR and assessment of risk of infection with Mycobacterium
tuberculosis prior to starting treatment with anti-TNF α.
Any patient with an abnormal chest radiograph or previous history of TB should be referred for
assessment by a specialist with an interest in TB.
Those with symptoms raising a suspicion of TB should be thoroughly investigated to exclude active
disease.
Any patient with active TB, either pulmonary or non-pulmonary, should receive standard
chemotherapy. They must complete 2 months full treatment before starting anti-TNF alpha
treatment.
Patients with an abnormal chest radiograph consistent with past TB, or a history or prior extra
pulmonary TB but who have received previous adequate therapy can be started on anti-TNF alpha
therapy but need to be monitored regularly.
Where there is an abnormal chest radiograph, or a history of prior pulmonary or extra pulmonary TB
not previously adequately treated, chemoprophylaxis with isoniazid for 6 months should be given
before commencing anti-TNF alpha treatment.
The BTS guidelines have not been updated to include recommendations regarding Quantiferon Gold
test and Elispot tests. Practice does vary between individual NHS trusts regarding who to test with
one of these, and which to use. However, the most accepted recommendations are that patients who
test positive with either of these should be treated with chemoprophylaxis (either isoniazid for 6
months, or dual therapy Rifampicin + INH for 2 months) at the same time as being started on anti-
TNF alpha treatment.
For patients with a normal chest radiograph who have not started immunosuppressive therapy, a
tuberculin test is helpful.
TNF-inhibitors should be stopped 2-4 wks before any major operation.
Stopping earlier may lead to disease flare and thus interfere with the surgery.
Treatment may be restarted postoperatively if there is no evidence of infection
Examples of anti-TNF alpha agents: o Etanercept, o Infliximab, o Adalimumab,
TNF therapy-Anti
1-soluble TNF receptor fusion protein
ETANERCEPT.
2-chimeric(mouse/human) anti-TNF-a
Ab…… INFLIXIMAB.
3-Fully humanized mAb
….ADALIMUMAB.
Etanercept SC: Soluble P75 TNF-a receptor fusion protein
o It is a recombinant human protein, acts as a decoy receptor for TNF-α, it is a fusion protein
that mimics the inhibitory effects of naturally occurring soluble TNF receptors.
o Dose: 25 mg SC administration twice weekly
o It can cause demyelination and risks of TB reactivation.
o It can be used alone in treatment RA or with methotrexate.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
o New onset and exacerbation of psoriasis.
o INFECTIONS:
Serious infections has been reported in 22 of 754 (2.9%)
Increased rate of lymphoma.
Pregnancy and breast feeding:
Are contraindicated.
o Also can be used in psoriasis and psoriatic arthritis.
o Used with caution in patients with asthma, renal imp.
Infliximab IV: Chimeric (human/murine) IgG 1 mono-clonal Ab to TNF-a.
Monoclonal antibody, binds to TNF-α and prevents it from binding with TNF receptors, IV
administration, risks include reactivation of tuberculosis
Infliximab should normally be used in combination with methotrexate and requires IV
infusion in a hospital setting.
If a patient is intolerant of methotrexate, etanercept (anti-TNF receptor antibody) and
adalimumab (humanised anti-TNF antibody) are alternatives to infliximab which can be
given as monotherapy. Infliximab is also used in active Crohn's disease unresponsive to
steroids.
SIDE EFFECT:
1-COMMON: headache, diarrhea, rash, pharyngitis, rhinitis, cough, URTI, UTI.
2-Infusion reaction (urticaria, pruritus, and chills)…..reduced by use of MTX.
3-INFECTIONS---TB:
The onset of TB typically soon after beginning of treatment, with 15% of cases detected by the 3
rd
infusion and 97% by the 6
th
infusion.
56%...extra-pulmonary
25%...disseminated.
FDA has recommended for patients considered for treatment with INF should be screened for LTBI :
By taking appropriate H/O TB exposure and by PPD skin testing.
In the case of positive PPD , anti-TB therapy being recommended prior to initiating INF.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Current standard include the use of INH or RIF for TB prophylaxis
4-Demyelinating disease
5-Development of human anti-chimeric molecule anti-bodies (HACA): 40%
The development of HACA was inversely related to the dose of INF.
Addition of low dose of MTX 7.5mg/week ….reduces the development of HACA.
6-ANTIBODY INDUCTION:
ANA and anti-ds-DNA AB were found in 45% and 33%, respectively of 42% patients who received 5
infusions of INF. AB to SM and RNA ……30%.
7-NEOPLASIA:In clinical trials 4 cases of lymphoma has been reported.
8-HEART FAILURE:
INF may worsen preexisting HF.
9-CNS VASCULITIS.
10-HEPATOTOXICITY.
11-CYTOPENIAS:PMS
Adalimumab: monoclonal antibody, SC administration
Tocilizumab: (anti-IL 6 receptor).
B-CELL TARGETED THERAPIES FOR RA:
B-cell directed therapies have the potential to ameliorate inflammatory arthritis through a variety of
mechanisms:
Impairing auto-anti-body production.
By disrupting B cell/T cell cross-talk.
By interfering with the antigen presentation or cytokine production.
Rituximab: ((B-cell depleting agents))
Anti-CD20 monoclonal antibody, results in B-cell depletion.
MECHANISM OF ACTION:
Lymphocytes of the B cell lineage undergo an orderly developmental process that includes
the surface expression of CD20, which is B lymphocyte –specific molecule , beginning at the
pre-B cell stage.
Expression of CD20 on the surface of B cells decrease or absent as B cell differentiate into
plasma cells.
RITUXIMAB causes B cell depletion through one of several mechanisms:
1. Fc receptor gamma-mediated Ab dependent cytotoxicity.
2. Complement mediated cell lysis.
3. Growth arrest.
4. B cell apoptosis.
Decreased or absent CD20 protein expression on surface of plasma cells is likely to account
for the resistance of these cells to rituximab.
As a consequence Ig levels are usually little changed, despite profound lymphopenia that
persists for months after a single course of treatment.
But level of auto antibodies with a potential role in disease pathogenesis are affected by B
cell depletion e.g RF in RA , ANCA in vascultis
Two 1g intravenous infusions are given two weeks apart.
B CELL DEPLETION:
Within 2-4 weeks B cells in peripheral
blood reach to undetectable levels.
Remain 6-12 months.
Ig levels:
A small proportion of patients may
have Ig levels below the normal levels.
AUTO-ANTIBODIES: RF is
significantly reduced.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
The most common side effects:
1) 1-INFUSION REACTIONS:
Common, hypotension, hypertension, skin rash , pruritus, nausea and back pain……..due
cytokine release syndrome.
2) INFECTIONS--- Severe CMV infection
3) 3-OTHER REACTIONS: Steven-johnson syndrome, Vesicubollous dermatitis ,Toxic epidermal
necrolysis.
4) 4-Human anti-chimeric antibodies: HACA
5) Allergic reactions: low BP and facial flushing during IV infusion.
6) Flu-like symptoms: high fever, chills, weakness, muscle aches, tiredness, dizziness and
headache during IV infusion.
7) Nausea and vomiting.
8) Tumour pain.
Uses: Non-Hodgkin lymphoma, Pure red cell aplasia, ITP, Evans syndrome, Rheumatoid
arthritis, Multiple sclerosis, SLE, Vasculitis.
Preventing and treating:
PREMEDICATIONS:
1-Acetaminophen 625 mg , diphenylhydramine 50mg before each infusion.
2- A single dose of methylprednisolone 100mg, 30 min. before beginning of infusion
3-Holding anti-hypertensive medications within 24 h of RIT infusion.
4-Initial infusion: the first infusion is begin at a rate of 50mg/h, the rate is increased by 50mg/h every
30min. To a maximum of 400mg/h.
MANGEMENT OF INFUSION REACTION:
1-Temporarily stopping RIT infusion, waiting for symptoms to subside, and then restarting infusion at
one-half of the initial rate.
An additional dose of acetaminphen 625mg orally and diphenylhydramine 50mg orally are given.
Additional treatment include: saline infusion, inhaled bronchodilator, IM epinephrine, and parenteral
GC.
RECOMMENDATION:
RIT is to be used for patients with RA who have persistent synoviitis despite an adequate
treatment of MTX and at least one anti-TNF agents used for a minimum of one month.
Abatacept:
Cytotoxic T-lymphocyte antigen 4 (CTLA 4) homologue,A soluble fusion protein comprising CTLA-4
and Fc protein of IgG1, CTLA-4 –Ig. It prevents CD28 from binding to its counter receptor, B7-1/B7-2.
Fusion protein that modulates a key signal required for activation of T lymphocytes
Leads to decreased T-cell proliferation and cytokine production
Given as an infusion , Not currently recommend by NICE
In Pregnancy:
Methotrexate (teratogenic) and NSAIDs (1st trimester, risk of abortion) so they are
absolutely contraindicated.
Prednisolone, Sulfasalazine and hydroxychloroquine are safe in pregnancy if these
are necessary for treatment of the mother's disease.
Sulfasalazine can be safely used prior to and during all stages of pregnancy, it is
compatible with breast feeding, although should be advised with cautions because
of the rare possibility that the mother is a slow acylator.
Azathioprine can be used in pregnancy if Sulfasalazine and hydroxychloroquine
are not controlling.
Prednisolone and hydroxychloroquine may be taken whilst breast-feeding.
Azathioprine, cyclophosphamide, methotrexate and cyclosporine are
contraindicated in breast-feeding mothers.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Azathioprine can be used during pregnancy if the benefits outweigh the risks.
Azathioprine can be continued at the same dose. No apparent congenital
malformations are known with doses up to 2mg/kg/day.
During pregnancy >>> continue current dose of azathioprine and add folic acid.
Breast feeding is not recommended with azathioprine.
Corticosteroids, the main alternative to azathioprine, are considered relatively safe in pregnancy
when used in low dose ˂ 20 mg daily. However they may increase the maternal risk of HTN,
oedema, gestational diabetes, osteoporosis, premature rupture of membranes (PROM), small-
forgestational-age babies (SGA), and increase in risk of cleft palate in foetus of first trimester. The
lowest possible steroid dose needed to control activity should be used in pregnancy if the choice is
to follow this option. The routine use of oral calcium and Vit D is recommended. Stress doses of
steroids should be used during labour and delivery if the mother received steroids (even low dose)
for more than 2-3 weeks during pregnancy, and the neonate should be monitored for evidence of
adrenal insufficiency and infection.
2002 ACR
Establish diagnosis of RA early
Document baseline disease activity + damage
Estimate prognosis
Initiate therapy
a. Patient education
b. DMARDS within 3 months
c. Consider NSAID
d. Consider local / low dose systemic steroids
e. Physical therapy , occupational therapy
PERIODICALLY ASSESS THE DISEASE ACTIVITY
Adequate response with decreased disease activity
Inadequate response
Ongoing active disease after 3 months of
maximal therapy.
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DR MAGDI AWAD SASI RHEUMATOID ARTHRITIS DIAGNOSIS NOT TO BE MISSED 2016
Change /add DMARDS
METHTREXATE NAÏVE SUBOPTIMAL METHOTRXATE RESPONSE
MTX OTHER MONOTR COMBINATION THERAPY
Combination therapy other monoTR Biologies
MULTIPLE DMARDS FAILURE
Symptomatic/structural joint damage
SURGERY