Histiocytosis refers to a group of disorders involving abnormal proliferation of histiocytes (white blood cells). There are several types classified based on the involved cell: Langerhans cell histiocytosis, hemophagocytic lymphohistiocytosis, and malignant histiocytic disorders. Langerhans cell histiocytosis (LCH) is characterized by abnormal proliferation of Langerhans cells. It ranges from isolated lesions to multisystem disease. Pulmonary LCH mainly affects smokers. Treatment depends on risk classification and may include chemotherapy. Hemophagocytic lymphohistiocytosis (HLH) involves overactivation of histiocytes and lymphocytes damaging organs. It can be inherited

1. HISTEOCYTIC
DISORDES
Dr. Walaa Al-Hady
Senior specialist in pediatrics

2. O Histiocytosis is a general name for a
group of disorders or "syndromes" that
involve an abnormal increase in the
number of specialized white blood cells
that are called histiocytes.

4. Historical calssification of
hisiocytoses:
Dendertitic cell and dermal denderitic cell
disorders
O Langerhans cell hisiocytosis
O Juvenile xanthogranulomatosis
O Erdheim chester disease
Macrophage related disorders
O Hemophagocytic lymphohisteocytosis
O Familial erythrophagocytic lymphohistiocytosis
O Infection associated hemophagocytic syndrom
O Malignancy associated hemophagocytic syndrome
O Rosai Dorfman disease
Malignant histiocytic disorders
O Dendritic cell related histiocytic sarcoma
O Monocyte related (moncytic leukemia or sarcoma )
O Macrophage reated histiocytic sarcoma

5. LANGERHANS CELL
HISTIOCYTOSIS

6. LCH
O Langerhans cell histiocytosis (LCH) is an
abnormal clonal proliferation of Langerhans cells,
abnormal cells deriving from bone marrow and
capable of migrating from skin to lymph nodes.
O Symptoms range from isolated bone lesions to
multisystem disease .LCH is part of a group of
syndromes called Histiocytoses, which are
characterized by an abnormal proliferation of
histiocytes (a term for activated dendritic cells
and macrophages). These diseases are related
to other forms of abnormal proliferation of white
blood cells, such as leukemias and lymphomas.

7. Classification
O The disease spectrum results from clonal
accumulation and proliferation of cells
resembling the epidermal dendritic cells
called Langerhans cells, sometimes called
dendritic cell histiocytosis. These cells in
combination with lymphocytes,
eosinophils, and normal histiocytes form
typical LCH lesions that can be found in
almost any organ.

8. LCH is clinically divided into three groups:
O Unifocal
O multifocal unisystemic
O multifocal multisystemic

9. O Unifocal LCH,
also called eosinophilic granuloma, is a disease
characterized by an expanding proliferation of Langerhans
cells in one organ, where they cause damage called
lesions. It typically has no extraskeletal involvement.
It can appear as a single lesion in an organ, up to a large
quantity of lesions in one organ.
When multiple lesions are scattered throughout an organ,
it can be called a multifocal unisystem variety. When found
in the lungs, it should be distinguished from Pulmonary
Langerhans cell hystiocytosis .
When found in the skin it is called cutaneous single
system Langerhans cell LCH. This version can heal without
therapy in some rare cases. This primary bone involvement
helps to differentiate eosinophilic granuloma from other
forms of Langerhans Cell Histiocytosis (Letterer-Siwe or
Hand-Schüller-Christian variant.

11. OMultifocal unisystem
Seen mostly in children, multifocal unisystem
LCH is characterized by fever, bone lesions and
diffuse eruptions, usually on the scalp and in the
ear canals. 50% of cases involve the pituitary
stalk, often leading to diabetes insipidus. The
triad of diabetes insipidus, exophthalmos, and
lytic bone lesions is known as the Hand-
Schüller-Christian triad. Peak
onset is 2–10 years of age.

13. O Multifocal multisystem
also called Letterer-Siwe disease,
is an often rapidly progressing disease in
which Langerhans Cell cells proliferate in
many tissues. It is mostly seen in children
under age 2, and the prognosis is poor:
even with aggressive chemotherapy, the
five-year survival is only 50%.

15. OPulmonary Langerhans cell
histiocytosis (PLCH)
O Pulmonary Langerhans cell histiocytosis
(PLCH) is a unique form of LCH in that it
occurs almost exclusively in cigarette
smokers. It is now considered a form of
smoking-related interstitial lung disease.
PLCH develops when an abundance of
monoclonal CD1a-positive Langerhans
(immature histiocytes) proliferate the
bronchioles and alveolar interstitium, and this
flood of histiocytes recruits granulocytes like
eosinophils and neutrophils and
agranulocytes like lymphocytes further
destroying bronchioles and the interstitial
alveolar space that can cause damage to the
lungs.

16. Signs and symptoms
.
O LCH provokes a non-specific inflammatory
response, which includes fever, lethargy, and
weight loss. Organ involvement can also cause
more specific symptoms.
O Bone: The most-frequently seen symptom in both
unifocal and multifocal disease is painful bone
swelling. The skull is most frequently affected,
followed by the long bones of the upper extremities
and flat bones. Infiltration in hands and feet is
unusual. Osteolytic lesions can lead to
pathological fractures.
O Skin: Commonly seen are a rash which varies from
scaly erythematous lesions to red papules
pronounced in intertriginous areas. Up to 80% of
LCH patients have extensive eruptions on the
scalp.

18. O Bone marrow: Pancytopenia with superadded
infection usually implies a poor prognosis. Anemia
can be due to a number of factors and does not
necessarily imply bone marrow infiltration.
O Lymph node: Enlargement of the liver in 20%, spleen
in 30% and lymph nodes in 50% of Histiocytosis
cases.
O Endocrine glands: Hypothalamic pituitary axis
commonly involved. Diabetes insipidus is most
common.Anterior pituitary hormone deficiency is
usually permanent.
O Lungs: some patients are asymptomatic, diagnosed
incidentally because of lung nodules on radiographs;
others experience chronic cough and shortness of
breath.
O Less frequently gastrointestinal tract, central nervous
system, and oral cavity.

19. diagnosis

20. Treatment
O Patient with a single lesions may be
treated with local therapy.
O Multifocal disease require a systemic
chemotherapy.
O Recurrent of LCH after surgical
intervention may be considered multifocal
disease.
O The Histiocytic society LCH-III protocol
with vinblastine /prednisolone with 6mp for
HR LCH.

23. prognosis
Low risk LCH is almost never fatal.
Historic prognostic factors used to stratify
HR LCH therapy include;
1. Response to initial 6 -12 weeks of
therapy.
2. Age at diagnosis (<24 month 60%
mortality)
3. Number of organs involved at diagnosis.

24. HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS
HLH

25. HLH
O Hemophagocytic lymphohistiocytosis
(HLH) is a rare but potentially fatal
condition in which certain white blood cells
(histiocytes and lymphocytes) build up in
and damage organs, including the bone
marrow, liver, and spleen, and destroy
other blood cells.
O •HLH most commonly affects infants and
young children.

26. O Certain aspects of immune function, such
as natural killer cell and cytotoxic T-cell
activity, are abnormal in HLH.
O HLH may be inherited (familial) or caused
by another condition (secondary), such as
infection. Familial HLH usually affects
children under 1 year of age, while the
secondary form typically occurs after age
6. A genetic cause is identified in most,
but not all, cases of familial HLH.

29. Symptoms and Diagnosis
O The symptoms of HLH include:
O •Fever
O •Cytopenias
O •Neutropenia:
O •Anemia:
O •Thrombocytopenia:
O •Enlarged liver and/or spleen
O •Abdominal distension, abdominal pain
O •Weight loss, failure to thrive
O •Rash
O •Jaundice
O •Enlarged lymph nodes
O •Malaise

30. Differential dignosis
OGriscelli syndrome
O A major differential diagnosis of HLH is Griscelli
syndrome (type 2). This is a rare autosomal
recessive disorder characterized by partial
albinism, hepatosplenomegaly, pancytopenia,
hepatitis, immunologic abnormalities, and
lymphohistiocytosis.
O Three types of Griscelli syndrome are recognised:
Type 1 has neurologic symptoms and mutations in
MYO5A. Prognosis depends on the severity of
neurologic manifestations. Type 2 has mutations in
RAB27A and haemophagocytic syndrome, with
abnormal T-cell and macrophage activation . Type
3 has mutations in melanophilin and is
characterized by partial albinism.

32. diagnosis

35. OWho should be screened for
primary HLH mutations ?
 Patient with sever persistant disease.
 Patient with reactivation of disease
 Known family history of HLH/ recurrent
pregnancy losses.
 Presentation in infancy.

36. Treatment
 HLH treatment incorporate tampering
down the hyperinflammotry state with
steroid and chemotherapy.
 Children with HLH are sick at initial
presentation require ICU ,supportive
therapy.
 Patient will need pneumocystis' jirovecii
prophylaxis with trimethoprim
sulfamethaxazol and antifungal
prophylaxis.

41. OEmapalumab, A monoclonal
antibody against IFN ,has recently been
approved by the FDA for children and
adults with recurrent and refractory HLH.

42. prognosis
O Without treatment , FHLH is usually fatal
rapidly, with median survival of about 2
months.
O Chemotherapy and immunosuppressive
therapy may prolong survival in FHLH but
only stem cell transplantation may be
curative .

44. O 2 year old female named dawla with
 Fever
 Splenomegaly
 Pancytopenia
 Hemophagocytic lymphohistiocyte in BM
O Ferrittin 440 < 500
O Triglycerides 201 < 265
O CD25 ?
O NK cell ?
O Genetic molecular study?