57: Intercellular Immunoglobulin (Ig) A Dermatosis (IgA Pemphigus) Flashcards
What are the two major types of IgA dermatosis (IAD)?
- Subcorneal pustular dermatosis (SPD) type
- Intraepidermal neutrophilic IgA (IEN) type
What is the hallmark for diagnosing various autoimmune bullous diseases (AIBDs)?
Detection of autoantibodies to the skin by immunofluorescence, in addition to clinical and histopathologic assessments.
What are the major autoantigens associated with IgA dermatosis?
- Desmogleins (Dsg)
- Desmocollins (Dsc)
- Cadherin-type cell-to-cell adhesion molecules found in desmosomes
What are the treatment options for IgA dermatosis?
- Dapsone and systemic corticosteroids
- Other options include:
- Tetracycline
- Colchicine
- Plasmapheresis
- Retinoids
- Adalimumab
- PUVA
What is the average age of onset for IgA dermatosis?
Around 45.9 years, which is younger than other autoimmune bullous diseases (AIBDs).
What is the significance of desmocollins in the context of IgA dermatosis?
Desmocollins are transmembrane glycoproteins that are part of the desmosomal cadherin superfamily and are major autoantigens in IgA dermatosis.
What is the clinical significance of detecting IgA antibodies in IEN-type IgA dermatosis?
IgA antibodies in IEN-type IAD sera react with cell surfaces at the interdesmosomal area in keratinocytes, suggesting that an autoantigen for IEN-type IAD is a nondesmosomal protein.
What are the main autoantigens in IgA Pemphigus, and how do they differ between SPD-type and IEN-type?
The main autoantigens are desmogleins and desmocollins. SPD-type reacts mainly with Dsc1, while IEN-type reacts with Dsc1, Dsc2, or Dsc3.
What are the typical clinical features of Subcorneal Pustular Dermatosis (SPD)?
- Superficial flaccid pustules developed in the periphery of annular or herpetiform erythema on the entire body.
- Most prevalent in intertriginous areas such as axillae and groin.
- Lesions turn into erosions and crusts, leading to postinflammatory pigmentation.
- Nikolsky sign is usually absent.
- Clinical features are indistinguishable from classical SPD without IgA autoantibodies.
- SPD-type IAD never develops mucous membrane lesions.
What distinguishes Intraepidermal Neutrophilic IgA Dermatosis (IEN) from other types of IgA Pemphigus?
- Characterized by demarcated atypical pustular lesions scattered on the entire body.
- Relatively deep pustules develop on the slightly elevated periphery of annular erythema, generating a ‘sunflower-like’ configuration.
- IEN-type shows oral mucosal lesions, which is a key distinguishing feature.
What are the histopathological findings associated with Pemphigus Foliaceus (PF)?
- Shows either IEN-type IAD intraepidermal neutrophilic pustules in the entire epidermis or PF-like acantholytic blister in the upper epidermis.
What is the significance of Direct Immunofluorescence (DIF) in diagnosing IgA Pemphigus?
- DIF is essential for detecting in vivo bound IgA autoantibodies using perilesional skin biopsy.
- A negative result for DIF raises serious doubts about the diagnosis of IAD.
What associated diseases are frequently found in patients with Intraepidermal Neutrophilic IgA Dermatosis (IEN)?
- Ulcerative colitis is the underlying disease most frequently found in IAD, associated with either IEN-type IAD or PV-type IAD.
- Multiple myeloma or B-cell lymphoma is also associated with IAD.
What are the differences in IgA deposition patterns in Direct Immunofluorescence (DIF) for different types of IgA Pemphigus?
Type | IgA Deposition Pattern |
|——|———————-|
| SPD | Uppermost epidermis |
| IEN | Entire epidermis |
| PVeg | Various levels in the epidermis, depending on autoantigens |
| PF | Stronger in the upper epidermis, entire epidermis |
| PV | Lower epidermis |
A patient with IgA Pemphigus has severe oral mucosal lesions and paraneoplastic pemphigus-like features. What subtype is this, and what is the prognosis?
This is an Undetermined-type IgA Pemphigus. The prognosis is generally better than classical IgG pemphigus but can be refractory.
A patient presents with superficial flaccid pustules in the axillae and groin, which later turn into erosions and crusts. What type of IgA Pemphigus is most likely, and what diagnostic test would confirm it?
The patient most likely has Subcorneal Pustular Dermatosis (SPD)-type IgA Pemphigus. Direct Immunofluorescence (DIF) showing IgA deposition in the uppermost epidermis would confirm the diagnosis.
A patient with IgA Pemphigus shows oral mucosal lesions and atypical pustular lesions with a sunflower-like configuration. What subtype is this, and what histopathologic feature would you expect?
This is Intraepidermal Neutrophilic IgA Dermatosis (IEN)-type. Histopathology would show intraepidermal neutrophilic pustules in the middle or entire epidermis.
A patient diagnosed with IgA Pemphigus has vegetating lesions with erosions in the intertriginous areas and scalp. What subtype is this, and what is the associated histopathologic finding?
This is Pemphigus Vegetans (PVeg)-type. Histopathology would show PVeg-like acanthosis with intraepidermal neutrophilic/eosinophilic pustules.
What is the primary difference in IgA deposition between SPD-type and IEN-type IgA Pemphigus as seen in Direct Immunofluorescence (DIF)?
In SPD-type, IgA deposits are found in the uppermost epidermis, while in IEN-type, IgA deposits are found throughout the entire epidermis.
A patient with IgA Pemphigus shows IgA reactivity exclusively with Dsg1 in ELISA. What subtype does this indicate, and what clinical features might mimic this condition?
This indicates Pemphigus Foliaceus (PF)-type. Clinical features might mimic either PF or IEN-type IgA Pemphigus.
A patient with IgA Pemphigus has IgA reactivity exclusively with Dsg3 in ELISA and presents with oral mucosal erosive lesions. What subtype is this, and what histopathologic features might be observed?
This is Pemphigus Vulgaris (PV)-type. Histopathology might show IEN-type pustules containing neutrophils or eosinophils in the entire epidermis, or PV-like suprabasilar acantholytic blisters.
What underlying diseases are most frequently associated with IEN-type and PV-type IgA Pemphigus?
Ulcerative colitis is most frequently associated with IEN-type and PV-type IgA Pemphigus.
What is the significance of IgA titers in Indirect Immunofluorescence (IIF) for IgA Pemphigus, and how does it compare to Direct Immunofluorescence (DIF)?
IgA titers in IIF are semiquantitative and may help determine disease activity and treatment options, but their correlation with disease activity is less apparent than in classical IgG pemphigus. DIF is nonquantitative but more sensitive.
A patient with IgA Pemphigus has a history of multiple myeloma. What is the likely pathogenesis, and which diagnostic test would confirm the association?
The pathogenesis likely involves B-cell or plasma cell proliferative disorders triggering IgA Pemphigus. Elevated total serum IgA levels and DIF showing IgA deposition would confirm the association.
What are the histopathologic differences between SPD-type and PVeg-type IgA Pemphigus?
SPD-type shows subcorneal neutrophilic pustules in the uppermost epidermis, while PVeg-type shows PVeg-like acanthosis with intraepidermal neutrophilic/eosinophilic pustules.
What clinical features differentiate SPD-type IgA Pemphigus from classical SPD without IgA autoantibodies?
SPD-type IgA Pemphigus is clinically indistinguishable from classical SPD without IgA autoantibodies, but DIF showing IgA deposition in the uppermost epidermis differentiates them.
A patient with IgA Pemphigus shows IgA reactivity with Dsg1 in ELISA. What subtype is this, and what histopathologic feature would confirm the diagnosis?
This is Pemphigus Foliaceus (PF)-type. Histopathology would show PF-like acantholytic blister in the upper epidermis.
A patient with IgA Pemphigus shows IgA reactivity with Dsc1 in ELISA but not with Dsc2 or Dsc3. What subtype is this, and what clinical features might be observed?
This is SPD-type IgA Pemphigus. Clinical features include superficial flaccid pustules in intertriginous areas.
What are the clinical and histopathologic features of IEN-type IgA Pemphigus?
Clinically, IEN-type shows atypical pustular lesions with a sunflower-like configuration. Histopathology shows intraepidermal neutrophilic pustules in the middle or entire epidermis.
A patient with IgA Pemphigus shows IgA reactivity with Dsg3 in ELISA. What subtype is this, and what clinical features might mimic this condition?
This is Pemphigus Vulgaris (PV)-type. Clinical features might mimic either PV or IEN-type IgA Pemphigus.
What are the main differences in clinical features between SPD-type and PVeg-type IgA Pemphigus?
SPD-type shows superficial pustules in intertriginous areas, while PVeg-type shows vegetating lesions with erosions in intertriginous areas and the scalp.
What is the significance of using serially diluted patient sera in Indirect Immunofluorescence (IIF) for IgA Pemphigus?
Serially diluted sera in IIF provide a semiquantitative measure of IgA titers, which may help determine disease activity and treatment options.
A patient with IgA Pemphigus shows IgA reactivity with Dsg1 in ELISA and presents with superficial pustules. What subtype is this, and what histopathologic feature would confirm the diagnosis?
This is Pemphigus Foliaceus (PF)-type. Histopathology would show PF-like acantholytic blister in the upper epidermis.
What is the significance of using normal human skin or monkey esophagus as substrates in Indirect Immunofluorescence (IIF) for IgA Pemphigus?
These substrates help detect IgA reactivity to keratinocyte cell surfaces, but the sensitivity of IIF is lower than DIF.
What are the clinical features that distinguish Subcorneal Pustular Dermatosis (SPD) from other types of IgA Pemphigus?
SPD presents with superficial flaccid pustules that develop in the periphery of annular or herpetiform erythema, primarily in intertriginous areas like the axillae and groin. These pustules can turn into erosions and crusts, leading to postinflammatory pigmentation. Notably, Nikolsky sign is usually absent, and SPD-type IgA Dermatosis (IAD) never develops mucous membrane lesions.
How does the histopathological finding of Intraepidermal Neutrophilic IgA Dermatosis (IEN) differ from that of Subcorneal Pustular Dermatosis (SPD)?
IEN is characterized by intraepidermal neutrophilic pustules located in the middle or entire epidermis.
What are the clinical features of IgA Dermatosis?
Pustules can turn into erosions and crusts, leading to postinflammatory pigmentation. Nikolsky sign is usually absent, and SPD-type IgA Dermatosis (IAD) never develops mucous membrane lesions.
How does the histopathological finding of Intraepidermal Neutrophilic IgA Dermatosis (IEN) differ from Subcorneal Pustular Dermatosis (SPD)?
IEN is characterized by intraepidermal neutrophilic pustules located in the middle or entire epidermis, often accompanied by eosinophils and acantholytic cells. In contrast, SPD shows subcorneal neutrophilic pustules in the uppermost epidermis.
What is the significance of Direct Immunofluorescence (DIF) in diagnosing IgA Dermatosis?
DIF is crucial for detecting in vivo bound IgA autoantibodies using perilesional skin biopsy. A negative result in DIF raises serious doubts about the diagnosis of IgA Dermatosis.
What associated diseases are frequently found in patients with Intraepidermal Neutrophilic IgA Dermatosis (IEN)?
IEN is frequently associated with ulcerative colitis and may also be linked to multiple myeloma or B-cell lymphoma.
What laboratory tests are essential for diagnosing IgA Pemphigus?
Essential laboratory tests include histopathologic examination, Direct Immunofluorescence (DIF), Indirect Immunofluorescence (IIF), and Immunoblotting and ELISA.
What is the preferred diagnostic method for detecting IgA autoantibodies in IgA Dermatosis?
The preferred diagnostic method is IgA ELISA using mammalian recombinant proteins of Dsc1, Dsc2, and Dsc3.
What are the common treatment options for IgA Pemphigus?
Common treatment options include oral dapsone, other sulfonamides, systemic corticosteroids, and immunosuppressive agents.
How does the prognosis of IgA Dermatosis compare to classical IgG types of pemphigus?
IgA Dermatosis has a much better prognosis than classical IgG types of pemphigus, as it is rarely fatal.
What is the role of ELISA in the diagnosis of IgA Pemphigus?
ELISA is a quantitative method that is more sensitive than IIF or immunoblotting for detecting IgA autoantibodies.
What are the potential future therapeutic options for patients with intractable IgA Dermatosis?
Potential future therapeutic options include anti-CD20 monoclonal antibodies like Rituximab.
What is the significance of IgA reactivity in immunoblotting for diagnosing IgA Pemphigus?
Immunoblotting can identify autoantigens but is time-consuming and hazardous.
What does IgA reactivity with Dsc1, Dsc2, and Dsc3 in ELISA indicate?
This indicates a subtype other than SPD-type, as SPD-type reacts mainly with Dsc1.
What is the role of Complementary DNA (cDNA) transfection in diagnosing IgA Pemphigus?
cDNA transfection is a sensitive method for detecting IgA autoantibodies to Dsc1, Dsc2, and Dsc3.
What is the preferred first-line treatment for IgA Pemphigus?
The preferred first-line treatment is oral dapsone (50-200 mg/day).
What does recurrent skin lesions after 30 years of remission indicate in IgA Pemphigus?
This indicates that IgA Pemphigus is not fatal but is an extremely intractable disease.
What additional treatments could be considered for insufficient response to dapsone in IgA Pemphigus?
Additional treatments could include low-dose systemic corticosteroids, sulfonamides, or immunosuppressive agents.
What is the role of anti-CD20 monoclonal antibodies in treating IgA Pemphigus?
Anti-CD20 monoclonal antibodies may be considered for extremely intractable IgA Pemphigus.
What is the significance of using mammalian recombinant proteins in ELISA for diagnosing IgA Pemphigus?
Mammalian recombinant proteins improve sensitivity for detecting IgA autoantibodies.
What is the role of plasmapheresis in treating IgA Pemphigus?
Plasmapheresis is used to remove IgA autoantibodies in severe cases.
What subtype does IgA deposition in various epidermal layers suggest in IgA Pemphigus?
This suggests an Undetermined-type IgA Pemphigus.
What subtype does IgA deposition in the lower epidermis suggest in IgA Pemphigus?
This suggests Pemphigus Vulgaris (PV)-type.
What subtype does IgA deposition in the entire epidermis suggest in IgA Pemphigus?
This is Pemphigus Foliaceus (PF)-type.
What are the main differences in IgA deposition patterns between PF-type and PV-type IgA Pemphigus?
In PF-type, IgA deposition is stronger in the upper epidermis, while in PV-type, it is in the lower epidermis.
What are the clinical features that differentiate Major IgA Pemphigus from Minor IgA Pemphigus?
Major IgA Pemphigus presents with superficial pustules, while Minor IgA Pemphigus shows atypical pustular lesions.
How do the histopathologic features differ between Major and Minor IgA Pemphigus?
Major IgA Pemphigus shows subcorneal neutrophilic pustules, while Minor shows IEN-like intraepidermal pustules.
What is the significance of DIF findings in differentiating types of IgA Pemphigus?
DIF findings help confirm the diagnosis and understand the disease’s severity.
What role do autoantibodies play in the classification of IgA Pemphigus types?
Autoantibodies indicate the specific subtype and guide treatment options.
