58: Linear Immunoglobulin A Dermatosis and Chronic Bullous Disease of Childhood Flashcards
What is the typical age of onset for Linear IgA Dermatosis (LAD)?
Typically occurs after the 4th decade of life.
What is the clinical presentation of Chronic Bullous Disease of Childhood (CBDC)?
Clinical presentation includes tense bullae in the perineum and perioral regions, often described as a ‘cluster of jewels’. New lesions may appear around the periphery of previous lesions with a collarette of blisters.
What is the drug association commonly linked with Linear IgA Dermatosis (LAD)?
LAD is associated with many drugs, including vancomycin.
What is the prognosis for patients with Chronic Bullous Disease of Childhood (CBDC)?
Patients with CBDC often experience spontaneous remissions within 2 years.
What immunopathological feature is common to both Linear IgA Dermatosis (LAD) and Chronic Bullous Disease of Childhood (CBDC)?
Both conditions are defined by the presence of a homogenous linear band of IgA at the dermal-epidermal basement membrane zone.
What is the predominant IgA subclass found in the skin of patients with Linear IgA Dermatosis (LAD)?
The predominant IgA subclass in the skin is almost exclusively IgA1.
What findings were revealed by immunoelectron microscopy studies regarding the location of IgA in the skin for LAD and CBDC?
For LAD, IgA was found in the lamina lucida region of the BMZ, below the lamina densa, and above and below the lamina densa. For CBDC, IgA was found either in the lamina lucida or a sublamina densa location.
What is the clinical presentation of CBDC in children?
CBDC in children presents with tense bullae in the perineum and perioral regions, often forming a ‘cluster of jewels.’
What is the significance of TNF2 allele in LAD?
The TNF2 allele is found with increased frequency in both adults and children with LAD.
A 45-year-old patient presents with tense bullae and a history of vancomycin use. What is the likely diagnosis, and what is the first-line treatment?
The likely diagnosis is Linear IgA Dermatosis (LAD), potentially drug-induced by vancomycin. The first-line treatment is dapsone.
A 4-year-old child presents with tense bullae in the perineum and perioral regions, described as a ‘cluster of jewels.’ What is the diagnosis, and what is the prognosis?
The diagnosis is Chronic Bullous Disease of Childhood (CBDC). The prognosis is generally good, with most children going into remission within 2 years.
What are the differences in clinical presentation between LAD and CBDC?
LAD often mimics dermatitis herpetiformis with pruritic papules and vesicles, while CBDC is characterized by tense bullae in the perineum and perioral regions, often forming a ‘cluster of jewels.’
What is the role of immunoelectron microscopy in diagnosing LAD and CBDC?
Immunoelectron microscopy helps determine the exact location of IgA in the skin, revealing distinct patterns of immunoreactants in the lamina lucida or sublamina densa.
A patient with LAD has IgA deposits in the skin. What subclass of IgA is most commonly found?
The IgA deposits are almost exclusively IgA1.
A patient with LAD has additional deposits of IgG and C3. Is this common in drug-induced LAD?
No, C3 deposits are not found in drug-induced LAD in adults.
What is the typical age of onset for LAD and CBDC?
LAD typically occurs after the 4th decade of life, while CBDC most often presents before the age of 5.
What is the significance of HLA-B8 in LAD and CBDC?
HLA-B8 is associated with both LAD and CBDC, with up to 76% of CBDC patients expressing HLA-B8.
What is the role of indirect immunofluorescence (IIF) in diagnosing LAD?
IIF demonstrates low-titer IgA antibodies against the epidermal side of split skin, helping to confirm the diagnosis of LAD.
What are the clinical features of drug-induced LAD?
Drug-induced LAD may present with erythema multiforme-like, toxic epidermal necrolysis-like, or morbilliform patterns, often resolving with drug discontinuation.
What is the significance of the lamina lucida in LAD?
The lamina lucida is a common site for IgA deposition in LAD, as revealed by immunoelectron microscopy.
What are the key clinical presentations of Linear IgA Dermatosis (LAD) and Chronic Bullous Disease of Childhood (CBDC)?
LAD: Clinical presentation may mimic dermatitis herpetiformis (DH), bullous pemphigoid (BP), and cicatricial pemphigoid.
CBDC: Characterized by tense bullae in the perineum and perioral regions, often described as a ‘cluster of jewels’. New lesions may appear around the periphery of previous lesions with a collarette of blisters.
How do the drug associations differ between Linear IgA Dermatosis (LAD) and Chronic Bullous Disease of Childhood (CBDC)?
LAD: Associated with many drugs, including vancomycin. Can occur in association with inflammatory bowel disease (IBD) but is only rarely associated with gluten-sensitive enteropathy.
CBDC: Less clear drug associations, but studies suggest it may represent a different presentation of the same disease process as LAD.
What is the significance of HLA associations in Linear IgA Dermatosis (LAD) and Chronic Bullous Disease of Childhood (CBDC)?
LAD: Conflicting results regarding HLA-B8 frequency; some studies show increased frequency while others do not.
CBDC: Up to 76% of patients express HLA-B8, with increased frequencies of HLA-DR3 and HLA-DQ2 not seen in adults with LAD, indicating a potential difference in immunogenetic profiles between the two conditions.
What are the immunopathological features of Linear IgA Dermatosis (LAD) and Chronic Bullous Disease of Childhood (CBDC)?
Both conditions are characterized by:
- A homogenous linear band of IgA at the dermal-epidermal basement membrane zone.
- A minority of patients may have additional deposits, primarily IgG and occasionally C3.
- LAD shows almost exclusively IgA1, while CBDC may show IgA in either the lamina lucida or sublamina densa location, suggesting multiple antigens may be involved in both conditions.
What is the predominant antigenic target in patients with Linear IgA Dermatosis (LAD)?
The predominant antigenic target in patients with LAD is the BP 180 antigen (collagen XVII).
How do the clinical findings of Linear IgA Dermatosis (LAD) compare to dermatitis herpetiformis (DH)?
Clinical findings of LAD are heterogeneous and often indistinguishable from dermatitis herpetiformis (DH), presenting with combinations of annular or grouped papules, vesicles, and bullae, typically with a symmetric distribution and may be very pruritic.
What are the mucosal manifestations associated with Linear IgA Dermatosis (LAD)?
Mucosal manifestations in LAD can range from:
1. Largely asymptomatic oral ulcerations and erosions
2. Severe oral disease alone
3. Severe conjunctivitis and oral disease typical of cicatricial pemphigoid.
What is the relationship between Linear IgA Dermatosis (LAD) and gluten-sensitive enteropathy?
Numerous investigators have been unable to show that the majority of patients with LAD have significant evidence of the villous atrophy characteristic of dermatitis herpetiformis (DH). Clinical manifestations have not been controlled by the use of a gluten-free diet.
What are the common clinical findings in Chronic Bullous Disease of Childhood (CBDC)?
Common clinical findings in CBDC include:
- Development of tense bullae, often on an inflammatory base
- Most frequently occurring in the perineum and perioral region
- Lesions may appear in clusters, giving a ‘cluster of jewels’ appearance
- Significant pruritus and/or burning of the skin with the development of lesions.
A patient with LAD has circulating IgA antibodies. What is the most common antigenic target for these antibodies?
The most common antigenic target is BPAG2 (collagen XVII).
What are the common sites of cutaneous involvement in LAD?
Common sites include extensor surfaces such as elbows, knees, and buttocks.
What is the significance of epitope spreading in LAD?
Epitope spreading suggests that IgA may bind to multiple antigenic targets, but the clinical significance is not fully established.
What is the significance of the 120-kDa ectodomain of BPAG2 in LAD?
The 120-kDa ectodomain of BPAG2 is a target for autoantibodies in LAD, similar to bullous pemphigoid.
A patient with LAD presents with mucosal involvement. What are the possible mucosal manifestations?
Mucosal manifestations can range from asymptomatic oral ulcerations and erosions to severe conjunctivitis and oral disease typical of cicatricial pemphigoid.
What is the significance of the 97-kDa protein in LAD and CBDC?
The 97-kDa protein is identical to a portion of the extracellular domain of the 180-kDa BP antigen (BPAG2 or collagen XVII), essential for anchoring basal keratinocytes to the epidermal basement membrane.
A patient with LAD develops a febrile illness with arthritis and generalized malaise. What is the likely cause?
This presentation is rare but can occur in LAD, potentially triggered by drug-induced LAD or an acute systemic reaction.
What is the clinical significance of the NC-16A region of collagen type XVII in LAD?
The NC-16A region is a target for IgA antibodies and T cells in LAD, explaining the overlap in clinical and histologic features with bullous pemphigoid.
What is the significance of LAD 285 in LAD?
LAD 285 is a 285-kDa protein that serves as an antigenic target in some patients with LAD.
What are the clinical findings associated with Linear IgA Dermatosis (LAD) and how do they compare to dermatitis herpetiformis (DH)?
Clinical findings of LAD are heterogeneous and often indistinguishable from DH, presenting with:
- Combinations of annular or grouped papules, vesicles, and bullae
- Symmetric distribution on extensor surfaces (elbows, knees, buttocks)
- Variable pruritus, generally less severe than DH
- Some may present with larger bullae, resembling BP or EBA.
In contrast, DH typically shows more severe pruritus and a different distribution pattern.
What are the specific antigenic targets identified in patients with Linear IgA Dermatosis (LAD)?
Specific antigenic targets in LAD include:
- 97-kDa protein: Found in the lamina lucida, similar to the IgA localization in CBDC and LAD.
- BP180 (collagen XVII): The predominant antigenic target, essential for anchoring basal keratinocytes to the epidermal basement membrane.
- NC-16A region of collagen type XVII: Targeted by IgA antibodies and T cells in LAD, similar to IgG and T cells in BP.
- 285-kDa protein: Found in some patients with LAD, not identified as BP or Type VII collagen.
How does the mucosal involvement in Linear IgA Dermatosis (LAD) differ from that in Chronic Bullous Disease of Childhood (CBDC)?
Mucosal involvement in LAD can range from:
- Largely asymptomatic oral ulcerations and erosions
- Severe oral disease or conjunctivitis, often seen in cicatricial pemphigoid.
In contrast, CBDC shows less frequent mucosal involvement and typically presents with a good prognosis.
What are the disease associations related to Linear IgA Dermatosis (LAD) and gluten-sensitive enteropathy?
Investigations have shown that:
- The majority of patients with LAD do not exhibit significant evidence of villous atrophy characteristic of dermatitis herpetiformis (DH).
- Clinical manifestations in LAD have not been controlled by a gluten-free diet.
- Transglutaminase, which is commonly elevated in untreated gluten-sensitive enteropathy and DH, has not been found in most patients with LAD.
What are the implications of drug-induced Linear IgA Dermatosis (LAD) and its clinical presentation?
Drug-induced LAD can present with:
- EM-like and TEN-like presentations with widespread bullae.
- Localized palmar and morbilliform variants.
- Significant association with drugs such as vancomycin, lithium, and phenytoin.
Recovery has been noted with the discontinuation of the offending drug, and patients may benefit from dapsone therapy.
What is the most common drug associated with the development of Linear IgA Dermatosis (LAD)?
Vancomycin is the most common drug associated with the development of LAD, and it is the most common nonimmediate hypersensitivity reaction to this drug.
What are the key histopathological features of early lesions in Linear IgA Dermatosis (LAD)?
Early lesions in LAD are characterized by:
1. Subepidermal bulla with collections of neutrophils along the basement membrane, often at the papillary tips.
2. Mild lymphocytic infiltrate may be present around superficial dermal blood vessels without evidence of neutrophilic vasculitis.
3. Infiltrate is composed of eosinophils and neutrophils as the major component.
What are the treatment options for patients with Linear IgA Dermatosis (LAD)?
Treatment options for LAD include:
1. First-line: Dapsone
2. Second-line: Sulfapyridine
3. Adjuvant treatments:
- Mycophenolate mofetil as a steroid-sparing agent
- Trimethoprim-sulfamethoxazole for additional support
4. Low-dose prednisone may be required for some patients to suppress blister formation.
5. Gluten-free diet: Majority of patients cannot control their skin disease with this diet.
What is the clinical significance of the findings in the differential diagnosis of Linear IgA Dermatosis (LAD)?
The differential diagnosis of LAD is clinically significant because:
- LAD closely mimics the clinical pattern of Dermatitis Herpetiformis (DH).
- It must be differentiated from Bullous Pemphigoid (BP), cicatricial pemphigoid, EBA, and rarely, TEN.
- Diagnostic findings of linear IgA at the basement membrane can distinguish LAD from BP and other conditions, particularly in the absence of IgG and C3.
What is the role of IVIG in treating CBDC?
IVIG has been proposed for rare patients with CBDC who are unresponsive to or intolerant of dapsone.
What is the role of sulfonamides in treating LAD?
Sulfonamides, such as sulfapyridine, are effective alternatives to dapsone in treating LAD.
What is the role of DIF in diagnosing LAD?
Direct immunofluorescence (DIF)
What can distinguish LAD from BP and other conditions?
A at the basement membrane can distinguish LAD from BP and other conditions, particularly in the absence of IgG and C3.
What is the role of DIF in diagnosing LAD?
Direct immunofluorescence (DIF) shows linear IgA deposits at the basement membrane, distinguishing LAD from other blistering diseases.
What is the prognosis for LAD in adults?
The course of LAD in adults is unpredictable, with some experiencing spontaneous remission and others having persistent disease.
What alternative treatments can be considered for a patient with LAD unresponsive to dapsone?
Alternative treatments include low-dose prednisone, mycophenolate mofetil, or trimethoprim-sulfamethoxazole.
What histopathological findings are characteristic of LAD and CBDC?
Histopathological findings include subepidermal bulla with collections of neutrophils along the basement membrane, often accumulating at the papillary tips.
Can a gluten-free diet control skin disease in a patient with LAD who has a history of gluten-sensitive enteropathy?
No, the majority of patients with LAD cannot control their skin disease with a gluten-free diet.
What is the most common drug associated with drug-induced LAD?
The most common drug associated with drug-induced LAD is vancomycin.
What is the prognosis for CBDC in children?
The prognosis is generally good, with most children going into remission within 2 years of onset.
What are the common triggers for LAD?
Common triggers include drugs like vancomycin, lithium, and phenytoin, as well as physical exposures like ultraviolet light.
What is the role of dapsone in treating LAD and CBDC?
Dapsone is the first-line treatment for both LAD and CBDC, often producing a dramatic response within 24-48 hours.
What are the histopathological differences between LAD and dermatitis herpetiformis (DH)?
LAD patients tend to have fewer papillary microabscesses and a more diffuse infiltrate of neutrophils at the basement membrane zone compared to DH.
What are the potential systemic associations of LAD?
Systemic associations include ulcerative colitis, Crohn’s disease, and rarely, lymphoid malignancies.
What is the role of topical tacrolimus in treating CBDC?
Topical tacrolimus may be useful in minimizing systemic therapy for CBDC.
What is the role of mycophenolate mofetil in treating LAD?
Mycophenolate mofetil is used as a steroid-sparing agent in patients unresponsive to dapsone or prednisone.
What is the relationship between LAD and gluten-sensitive enteropathy?
Unlike dermatitis herpetiformis, LAD is not consistently associated with gluten-sensitive enteropathy.
What are the common drugs associated with the development of Linear IgA Dermatosis (LAD)?
The most common drug associated with LAD is vancomycin, along with other drugs like lithium, phenytoin, sulfamethoxazole-trimethoprim, furosemide, atorvastatin, captopril, diclofenac, ketoprofen, and infliximab.
What is the significance of identifying the causative agent in drug-induced Linear IgA Dermatosis (LAD)?
Identifying the causative agent in drug-induced LAD is crucial because it can help in managing the condition effectively.
How does the clinical presentation of Chronic Bullous Disease of Childhood (CBDC) differ from Linear IgA Dermatosis (LAD)?
CBDC typically presents as a self-limited disease, often resolving within 2 years, while LAD can have a more unpredictable course.
What are the histopathological features observed in early lesions of Linear IgA Dermatosis (LAD)?
Early lesions of LAD show subepidermal bullae with collections of neutrophils along the basement membrane.
What treatment options are available for patients with Linear IgA Dermatosis (LAD) who do not respond to standard therapies?
Options include mycophenolate mofetil as a steroid-sparing agent and trimethoprim-sulfamethoxazole.
What antibiotics have been suggested for use in cases of Linear IgA Dermatosis (LAD)?
Several case reports suggest the use of sulfonamides, dicloxacillin, and erythromycin.
What was the outcome of treating 7 children with LAD using flucloxacillin?
In a case series, 7 children with LAD were treated with flucloxacillin, resulting in improvement, with 4 children achieving remission within 3 months.
What is a potential consideration regarding the remission of patients treated for LAD?
Spontaneous remission in these patients cannot be ruled out.
What are the clinical implications of using antibiotics such as sulfonamides, dicloxacillin, and erythromycin in the treatment of Linear IgA Dermatosis (LAD)?
These antibiotics may be beneficial in treating LAD, but spontaneous remission cannot be ruled out.
How does the clinical presentation of Linear IgA Dermatosis (LAD) compare to Drug-Induced IgA and Chronic Bullous Disease of Childhood (CBDC)?
The clinical presentation varies significantly among these conditions.
