2. MEMBER REGISTRATION NO.
TRAVOR MUSINGUZI 2021-08-07385
KAYANJA JOAN 2021-08-07390
B. A. DANIELA HAPPY NOSHIPO 2021-08-07391
ALLAN OKURE 2021-08-07394
SIMON PETER MAGWALI 2021-08-07405
3. SKIN IMMUNE DISEASES
INTRODUCTION
• A set of skin conditions known as immune-mediated skin diseases are brought on by an
aberrant immune response to normally benign chemicals. In immune mediated skin illnesses,
the immune system accidentally assaults the healthy skin cells, resulting in inflammation and
skin damage. Normally, the immune system fights off things like germs and viruses.
• Only five autoimmune disorders have been mentioned in this manuscript out of the many that
exist.
• Psoriasis
• Acute Eczematous Dermatitis
• Pemphigus
• Bullous Pemphigoid
• Urticaria
4. Psoriasis
• A persistent inflammatory dermatosis with an autoimmune origin, psoriasis is a skin
condition. It is a widespread disorder that impacts 1% to 2% of persons in the US.
• The condition can affect people of any age. An associated arthritis that may be moderate
or may result in severe deformities like the joint abnormalities observed in rheumatoid
arthritis affects 15% of people with psoriasis.
• Any joint in the body may be affected, and it may be symmetrical or asymmetrical.
Additionally, myopathy, enteropathy, and acquired immunodeficiency syndrome (AIDS)
may also be linked to psoriasis.
5. Etiology of Psoriasis
• Psoriasis is an immune-mediated illness, which means that it is brought on by an overactive
immune system in your body. Immune cells become active in people with psoriasis and
release chemicals that trigger the rapid creation of skin cells. Because of this, the skin of those
who have the illness is irritated and scaly. Although scientists are unsure of the exact cause of
defective immune cell activation, they do know that genetic and environmental variables are
likely to be involved.
• Many psoriasis sufferers have a family history of the condition, and scientists have identified a
few genes that may play a role in its onset. Almost all of them contribute to how the immune
system works. Some external factors that may increase the chances of developing psoriasis
include:
• Infections, especially streptococcal and HIV infections.
• Certain medicines, such as drugs for treating heart disease, malaria, or mental health
problems.
• Smoking.
• Obesity.
6. Pathogenesis Of Psoriasis
• Psoriasis is thought to be caused by a combination of environmental and genetic variables,
including certain HLA gene variations, similar to other suspected autoimmune illnesses.
• Although the culpable antigens are still elusive, it appears that activated CD8+ cytotoxic
effector T cells and sensitized CD4+ Th1 and Th17 cell populations penetrate the skin and
aggregate in the epidermis. By encouraging the release of cytokines and growth factors that
promote keratinocyte proliferation and cause the recognizable lesions, these T cells may
produce an aberrant microenvironment.
• A cytokine "soup" dominated by Th1-type and Th17-type cytokines like IL-12, interferon, tumor
necrosis factor (TNF), and IL-17 is produced as a result of interactions between CD4+ T cells,
CD8+ T cells, dendritic cells, and keratinocytes.
• The fact that patients treated with TNF inhibitors typically experience excellent clinical
outcomes underlines the significance of these factors.
• Additionally, keratinocytes receive growth factors from lymphocytes, which may aid in the
thickening of the epidermis. Psoriatic lesions can be induced in susceptible individuals by local
trauma, a process known as the Koebner phenomenon, presumably because trauma sets in
motion a local inflammatory response that becomes self-perpetuating.
7. Clinical features
• A patchy rash that varies widely in how it looks from person to person, ranging from spots
of dandruff-like scaling to major eruptions over much of the body
• Rashes that vary in color, tending to be shades of purple with gray scale on brown or
Black skin and pink or red with silver scale on white skin
• Small scaling spots (commonly seen in children)
• Dry, cracked skin that may bleed
• Itching, burning or soreness
• Cyclic rashes that flare for a few weeks or months and then subside
8. Diagnosis
• The look of the skin is typically used to get a psoriasis diagnosis. Scaly, erythematous
plaques, papules, or patches of skin that may itch and hurt are typical skin features of
psoriasis.
• Usually, the diagnosis can be made without the use of any specialized blood tests or
diagnostic techniques.
• The differential diagnosis of psoriasis includes dermatological conditions similar in
appearance such as discoid eczema, seborrheic eczema, pityriasis rosea (may be
confused with guttate psoriasis), nail fungus (may be confused with nail psoriasis) or
cutaneous T cell lymphoma (50% of individuals with this cancer are initially misdiagnosed
with psoriasis).
• The rash of secondary syphilis is one example of a dermatological manifestation of a
systemic illness that might be mistaken for psoriasis.
9. Diagnosis Con’td.
• A skin biopsy or scrape may be done to confirm the diagnosis and rule out other
conditions if the clinical diagnosis is unclear. On microscopy, skin taken from a biopsy will
exhibit clubbed epidermal projections that interdigitate with the dermis. Another distinctive
histologic feature of psoriasis lesions is epidermal thickening. In psoriatic lesions, the
stratum granulosum layer of the epidermis is frequently absent or considerably reduced;
the skin cells from the topmost layer of skin are also aberrant because they never fully
mature. These superficial cells retain their nucleus in contrast to their mature
counterparts. When analyzing psoriatic joint or skin tissue under a microscope,
inflammatory infiltrates can frequently be seen. While inflammatory infiltrates of the
dermal layer of skin and joints are primarily composed of CD4+ T cells, epidermal skin
tissue impacted by psoriatic inflammation frequently has a high CD8+ T cell count.
10. Types Cont’d.
Types
Plaque psoriasis.
• Plaque psoriasis, the most prevalent type of psoriasis, results in scale-covered, dry,
elevated skin patches (plaques). They could be few or numerous. They typically show up
on the scalp, lower back, elbows, and knees.
• Depending on the skin tone, the patches have different colors. On dark or Black skin, the
afflicted skin may heal with transient color changes (post-inflammatory
hyperpigmentation).
Nail psoriasis.
• Pitting, irregular nail growth, and discolouration can all be brought on by psoriasis and
affect both fingernails and toenails.
• Nails with psoriasis may become detached from the nail bed and become loose
(onycholysis). The nail may break if the illness is severe.
11. Guttate psoriasis.
• Young people and children are most commonly affected with guttate psoriasis. Usually, a
bacterial infection, like strep throat, is what sets it off. Small, drop-shaped scaling lesions on
the trunk, arms, or legs are its telltale sign.
Inverse psoriasis.
• The groin, buttocks, and breast skin folds are mostly impacted by inverse psoriasis. It results
in scaly, inflammatory skin patches that get worse with friction and perspiration. This kind of
psoriasis may be brought on by fungi.
Pustular psoriasis.
• A unusual form of pustular psoriasis results in distinct pus-filled blisters. On the palms or
soles, it may appear in little patches or in larger ones.
Erythrodermic psoriasis.
• Erythrodermic psoriasis, the least frequent form of the condition, can cover the entire body in a
peeling rash that can itch or burn severely. It can be either acutely short-lived or chronically
long-lived.
12. Acute Eczematous Dermatitis
• One of the most prevalent skin conditions, acute eczematous dermatitis, is described by
the Greek word eczema, which means "to boil over," in vivid detail. Based on initiating
factors, eczematous dermatitis can be subdivided into the following categories:
(1) allergic contact dermatitis,
(2) atopic dermatitis,
(3) drug-related eczematous dermatitis,
(4) photoeczematous dermatitis, and
(5) primary irritant dermatitis.
13. Con’td
• Either a reaction to an internal circulating antigen (which may be obtained from eaten food
or a medicine) or an illness caused by an external application of an antigen (such as
poison ivy) are sometimes considered the "inside and outside jobs" of eczema. The
search for harmful compounds that can be eliminated from the environment is part of the
treatment process.
• Steroids used topically can stop the inflammatory reaction. Even while such treatments
are only palliative and do not cure eczema, they are nonetheless useful in stopping its
acute exacerbations, which if left untreated can become self-perpetuating.
14. Etiology
• Dermatitis is thought to be brought on by a mix of hereditary and environmental factors,
while the exact etiology is unknown.
Environmental
• According to the hygiene hypothesis, an unusually clean environment in childhood results
in an inadequate human microbiome, which is the root cause of asthma, eczema, and
other allergy illnesses. Studies on the epidemiology of asthma lend support to it.
• According to the concept, avoiding exposure to bacteria and other immune system
modulators during development raises the risk for asthma and allergies.
• While up to 5% of people have antibodies to home dust mites, it has been hypothesized
that eczema may occasionally represent an allergic reaction to the mites' excrement.
However, further research is needed to confirm this.
15. Con’td
Genetic
• A number of genes, including filaggrin, have been linked to eczema. OVOL1, ACTL9, and
IL4-KIF3A are three novel genetic variations connected to eczema discovered through
genome-wide investigations.
• There may be a hereditary link between eczema and celiac disease because it occurs
roughly three times more commonly in people with the disorder and nearly twice as
frequently in their relatives.
16. Pathogenesis
• Typically, T cell-mediated inflammatory responses (type IV hypersensitivity) cause
eczematous dermatitis.This has been thoroughly investigated in dermatitis caused by
contact antigens, such as urease from poison ivy.
• It is thought that substances applied to the skin operate as "haptens" that produce
neoantigens when they interact with self proteins.
• Langerhans cells absorb these antigens and transport them to draining lymph nodes via
cutaneous lymphatics.
• Here, they expose naive CD4+ T cells to the neoantigens, which activate them and cause
them to grow into effector and memory cells
17. Con’td
• Memory T cells that express homing molecules, such as common lymphocyte antigen and
specific chemokine receptors, move to cutaneous areas where antigen is located in
response to antigen reexposure.
• This process occurs within 24 hours and accounts for the initial erythema and pruritus that
characterize the acute, spongiotic phase of eczema.
• Langerhans cells within the epidermis play a central role in contact dermatitis, and
naturally factors that affect Langerhans cell function impact the inflammatory reaction.
18. Clinical features
• Various types of dermatitis have various symptoms.
• They can be cutaneous rashes, bumpy rashes, or blister-accompanied rashes.
• Despite the fact that each variety of dermatitis manifests differently, there are several
symptoms that are present in all of them, including redness, swelling, itching, and skin
lesions that may occasionally ooze and leave scars.
19. Con’td
• With each type of dermatitis, the skin location where the symptoms manifest, whether on
the neck, wrist, forearm, thigh, or ankle, tends to vary.
• The main sign of this illness is itchy skin, though the location may vary. Rarely, it could
show up on the vulva or scrotum, which are genital regions.
• This kind of dermatitis can have quite severe symptoms that fluctuate. In general, painful
irritant contact dermatitis is worse than itching.
20. Diagnosis
• Eczema is mostly diagnosed based on a history and physical examination.
• A skin biopsy can be performed in circumstances where it is unclear whether the condition
is dermatitis or not.
• Food allergies may frequently be misdiagnosed in people with eczema. The diagnosis of
allergic contact dermatitis is made via patch tests.
21. Pemphigus
• Autoantibodies, which lead to the breakdown of intercellular bonds within the epidermis and
mucosal epithelium, are the cause of the blistering condition known as pemphigus.
• The molecular mechanisms underlying keratinocyte adhesion can be better understood
through understanding the pathobiology of blistering disorders. Men and women are equally
affected by pemphigus, and the majority of cases occur in people between the ages of 40 and
60. There are multiple variants:
(1) pemphigus vulgaris,
(2) pemphigus vegetans,
(3) pemphigus foliaceus,
(4) pemphigus erythematosus, and
(5) paraneoplastic pemphigus.
• These disorders are usually benign, but in extreme cases can be fatal without treatment.
22. Con’td
• The mucosa and skin are affected by pemphigus vulgaris, which is by far the most
prevalent kind (accounting for more than 80% of cases globally).
• These areas are particularly affected include the scalp, face, axilla, groin, trunk, and
points of pressure. Oral ulcers may be the first sign, and they may last for months before
any skin involvement shows.
• Primary lesions are easily ruptured superficial vesicles and bullae that leave shallow
erosions covered in crust and dried serum.
• Rarely, pemphigus vegetans manifests as large, wet, verrucous (wart-like), vegetating
plaques scattered with pustules on the groin, axillae, and flexural surfaces instead of
blisters.
23. Con’td.
• A more benign variant of the disease, Pemphigus foliaceus, is native to Brazil (where it is
known as fogo selvagem) and sporadic elsewhere.
The mucous membranes are only occasionally affected; lesions are more frequently found
on the scalp, face, chest, and back.
Bullae are so superficial that they mostly manifest as erythematous and crusted patches,
which are actually superficial erosions at blister rupture sites.
• Pemphigus erythematosus is thought to be a localized, less severe variation of
pemphigus foliaceus that may only affect the malar region of the face in a manner
resembling lupus erythematosus.
• • The most frequent malignancy associated with paraneoplastic pemphigus is non-
Hodgkin lymphoma.
24. Etiology
• An autoimmune condition called pemphigus develops when the immune system destroys
healthy skin. Desmogleins are a class of immune proteins that immune molecules called
antibodies aim towards in order to connect nearby skin cells.
• Skin becomes brittle when these connections are damaged, and fluid can accumulate
between cell layers, resulting in blisters.
• The immune system typically defends the body against illness and infection. Although
scientists are unsure of what triggers the immune system to activate the body's own
proteins, they think that both hereditary and environmental factors may be at play.
• People who are susceptible due to their genetic make-up may get pemphigus as a result
of anything in their surroundings. Pemphigus can occasionally be brought on by a tumor
or by specific drugs.
25. Pathogenesis
• IgG autoantibodies against desmogleins, which disrupt intercellular adhesions and cause
blister formation, are the cause of all forms of pemphigus, an autoimmune illness.
• Lesions exhibit a distinctive net-like pattern of intercellular IgG deposition by direct
immunofluorescence.
• In pemphigus vulgaris, IgG is typically visible at all levels of the epithelium, whereas in
pemphigus foliaceus, it is typically more superficial.
• The location and intensity of the blisters seem to be explained by the distribution of
desmoglein 1 and 3 in the epidermis and whether or not there are autoantibodies against
one or both proteins.
26. Con’td
• The desmosomes' ability to serve as intercellular adhesives is predominantly disrupted by
the antibodies, however they may also operate indirectly by activating intercellular
proteases.
• Autoantibodies that recognize desmogleins or other proteins involved in intercellular
adhesion also contribute to the development of paraneoplastic pemphigus, which most
frequently occurs in the context of lymphoid neoplasms. Immunosuppressive drugs are
the mainstay of treatment for all types of pemphigus because they lower the levels of
pathogenic antibody titers.
27. Clinical features
• Blistering of the skin and, in some cases, mucosal areas, including the interior of the mouth, nose,
throat, eyes, and genitals, is the primary sign of pemphigus. The fragile blisters have a propensity to
break, leaving behind crusty sores. Blisters on the skin may group together to create raw-looking,
infected patches that exude copious amounts of fluid.
• Depending on the type of pemphigus, the symptoms can vary.
• Blisters from Pemphigus vulgaris frequently begin in the mouth but might subsequently appear on
the skin. The skin may become so thin that stroking it with a finger causes it to peel off. Additionally,
mucosal surfaces on the nose, throat, eyes, and genitalia may be impacted. The deep layer of the
epidermis is where blisters originate, and they are frequently uncomfortable.
• Skin alone is impacted by pemphigus foliaceus. Blisters frequently start off on the face, scalp, chest,
or upper back before spreading to other body parts' skin. Skin irritation can cause afflicted regions
to swell up and peel off in layers or scales. The higher layers of the epidermis are where the blisters
develop, and they may itch or hurt.
28. Diagnosis
• Pemphigus, a rare disorder, can be challenging to identify because blisters can also be
present with a number of more prevalent conditions. Your doctor could recommend that
you see a dermatologist who specializes in skin disorders. Your doctor will inspect your
skin and mouth while also discussing your medical history with you. In addition, you may
undergo tests, including:
• A skin biopsy. In this test, a piece of tissue from a blister is removed and examined under
a microscope.
• Blood tests. One purpose of these tests is to detect and identify antibodies in your blood
that are known to be present with pemphigus.
• An endoscopy. If you have pemphigus vulgaris, your doctor may have you undergo
endoscopy to check for sores in the throat. This procedure involves inserting a flexible
tube (endoscope) down your throat.
29. Bullous Pemphigoid
• Bullous pemphigoid typically affects elderly people and has a variety of clinical
manifestations.
• Sites of involvement include the lower abdomen, axillae, groin, flexor surfaces of the
forearms, and inner parts of the thighs. 10% to 15% of those who are affected have oral
lesions, which typically develop following cutaneous symptoms.
• Some patients exhibit significant pruritus along with urticarial plaques.
30. Etiology
• There are typically no definite triggering factors found in cases of bullous pemphigoid.
• It has been suggested that radiation therapy and exposure to ultraviolet light are potential
triggering factors.
• A number of medications, including furosemide, nonsteroidal anti-inflammatory medicines,
DPP-4 inhibitors, captopril, penicillamine, and antibiotics, have also been linked to the
onset of pemphigoid.
31. Pathogenesis
• Autoantibodies that bind to proteins necessary for basal keratinocytes to attach to the
basement membrane are what produce bullous pemphigoid.
• At the dermoepidermal interface, where specialized structures termed hemidesmosomes
connect basal keratinocytes to the underlying basement membrane, the majority of
antibody deposition takes place in a continuous linear pattern.
• Hemiddesmosomes include the so-called bullous pemphigoid antigens (BPAGs).
• There is evidence that antibodies against BPAG2, one such component, can result in
blistering. Additionally, pathogenic autoantibodies trigger complement, which causes
inflammation, the activation of neutrophils and eosinophils, and the breakdown of
epidermal attachments.
32. Clinical features
• In terms of clinical presentation, the initial lesions can have a rash that resembles hives
and is red and raised, but they can also be dermatitic, targetoid, lichenoid, nodular, or
even absent of a rash (essential pruritus).
• The inner thighs and upper arms are the most typical places for tense bullae to emerge,
but the trunk and extremities are usually also affected. The skin surface can be affected
everywhere. In a small percentage of cases, oral lesions are present.
• The illness may be acute, but it also has a range in duration, with phases of exacerbation
and remission, from months to years. Similar symptoms may also be present in other skin
conditions.
• However, because to the deeper antigenic targets in epidermolysis bullosa acquisita, milia
are more frequent.
• A more ring-like pattern with a central depression or bullae that have collapsed in the
center may be a sign of linear IgA illness. In contrast to pemphigus vulgaris, where it is
positive, Nikolsky's sign is negative.
33. Diagnosis
• In order to diagnose an illness, at least two of the following three criteria must be met:
(1) pruritus and/or predominant cutaneous blisters;
(2) linear IgG and/or C3c deposits (in an n- serrated pattern) by direct immunofluorescence
microscopy (DIF); and
(3) positive epidermal side staining by indirect immunofluorescence microscopy on human
salt-split skin (IIF SSS) on a serum sample.
• Routine ELISA or H&E staining tests don't improve an initial diagnosis.
34. Urticaria
• A common skin condition known as urticaria (hives) is typically brought on by localized
mast cell degranulation and is invariably accompanied by dermal microvascular
hyperpermeability.
• Wheals are pruritic, edematous plaques that are caused by this interaction of actions.
Urticaria and angioedema share similarities, and angioedema is defined by edema of the
deeper dermis and subcutaneous fat.
• All age groups are susceptible to urticaria, however between 20 and 40 is when it most
frequently happens. Individual lesions form and disappear in a matter of hours (often
under 24 hours), while episodes can extend for days or even months.
• Any place subject to pressure, such as the trunk, distal extremities, and ears, is prone to
urticarial outbreaks. Although persistent urticaria episodes may be a sign of an underlying
illness (such as Hodgkin lymphoma or collagen vascular diseases), this is not always the
case.
35. Etiology
• Many different environmental factors, such as medicines, foods, and physical agents, can
cause hives; in perhaps more than 50% of people with chronic hives of unknown cause, it
is due to an autoimmune reaction.
• Risk factors include having conditions such as hay fever or asthma.
36. Pathogenesis
• The most frequent cause of urticaria is mast cell release of vasoactive mediators in
response to an antigen.The various forms can be classified based on their dependence
on IgE antibody and mast cells, as follows:
• Dependent on mast cells and immunoglobulin E (IgE).
• This kind of urticaria is an illustration of a localized immediate hypersensitivity (type I)
reaction brought on by the binding of antigen to IgE antibodies that are linked to mast
cells through Fc receptors and occurs after exposure to many different antigens (pollens,
foods, medicines, and insect venom).
37. Con’td
• IgE-independent, mast cell-dependent. This subset is brought on by agents that directly
trigger mast cell degranulation, such as opioids, certain antibiotics, and radiographic
contrast agents.
• IgE-independent and mast cell-independent. These urticaria types are brought on by
regional variables that raise vascular permeability.
• One type is brought on by exposure to substances or medications like aspirin that stop
the formation of cyclo-oxygenase and arachidonic acid.
• Unknown is the precise mechanism by which aspirin causes urticaria. A second type,
hereditary angioneurotic edema, is brought on by an inherited lack of C1 inhibitor, which
causes an overactive complement system and the release of vasoactive mediators.
38. Clinical features
• Symptoms of chronic hives include:
• Batches of welts (wheals) that can arise anywhere on the body
• Welts that might be red, purple or skin-colored, depending on your skin color
• Welts that vary in size, change shape, and appear and fade repeatedly
• Itchiness (pruritus), which can be intense
• Painful swelling (angioedema) around the eyes, cheeks or lips
• Flares triggered by heat, exercise or stress
• Symptoms that persist for more than six weeks and recur often and anytime, sometimes
for months or years
39. Diagnosis
• Based on clinical signs and anamnesis, the diagnosis is quite straightforward.
• In addition, it can occasionally be mistaken for drug eruptions, viral rashes, connective
tissue diseases, photosensitive illnesses, urticaria pigmentosa, urticarial vasculitis, and a
number of syndromic illnesses.
• In order to determine the cause of the urticaria, it is crucial to acquire a thorough history
from the patient.
40. con’td
• The patient should be questioned regarding the beginning, growth, localisation of lesions,
overall complaints, dietary habits, stress levels, and regular or irregular drug use.
• Routine laboratory studies and allergy tests are not necessary in cases of acute urticaria.
• There is no requirement for laboratory investigations if there is no evidence to support a
diagnosis, according to a U.S.-published guideline [3]. Only 25% of acute urticaria
episodes progress to chronic urticaria over time.
41. REFERENCES
• James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin:
Clinical Dermatology (10th ed.). Saunders. pp. 191–7.
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Primary Care. 42 (4): 473–83.
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