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.
