Linear iga dermatosis L13.8

Rare, chronic, autoimmunological, blistering dermatosis with linear IgA and C3 deposition at the dermo-epidermal junction zone belonging to the pemphigoid group. Basically a distinction is made between:

• LAD in adult age:
  • idiopathic LAD
  • drug-induced LAD (e.g. by At1-receptor blockers)
• LAD in children = benign chronic bullous dermatosis in children

Incidence (for Germany and France): Approx. 0.02-0.05/100,000 inhabitants/year. In larger contingents of blistering diseases less than 1% of patients with linear IgA dermatosis are found.

• Basically, from an etiopathogenetic point of view, 2 forms of LAD in adults must be distinguished.
  • Idiopathic LAD: This variant is associated with other autoimmune diseases and malignant tumors.
  • Medicinal LAD: The following drugs have been described as triggering: vancomycin, diclofenac, glibenclamide, iodine, penicillin, piperacillin, interferon gamma, sulbactam, cytostatic drugs.
• IgA antibodies were detected with a high percentage (60% of cases), IgG antibodies with a lower percentage (30%) and less frequently both types of Ak (20%) against autoantigens.
• Target autoantigens are the 120 kDa protein LAD-1 (produced by proteolysis at the NH2-terminus of the extracellular domain of BP 180 = bullous pemphigoid antigen).
• IgA antibodies against BP230 are rarer. There are no differences in the occurrence of antibodies between adults and children(chronic bullous dermatosis of childhood).
• Ultrastructurally, the antigens can be detected on the anchoring fibrils of the lamina lucida and on the lamina densa.

Most frequent blistering disease of childhood, usually first occurring at the age of 2-4 years (average 2.7 years). Boys are more frequently affected in childhood (m:w= 1.78:1.0).

Onset in adulthood mostly between the 20-40th year of life and after the 6th decade (in larger contingents the average age of adults was around 60 years). In adulthood w:m= 2:1

trunk, here without special predilection sites, possibly with emphasis on the sacral region, the groin and anogenital region. This (classical large-bubble form) is not distinguishable from the bullous pemphigoid in its distribution pattern.

Extremities including the back of the hand and palms may be affected.

Frequently the face (especially perioral and ears) and/or the capillitium are affected.

Variants with clinical (small vesicles) analogy to dermatitis herpetiformis show a stretched-sided emphasis (elbow, sacral region) of small vesicles grouped in herpetiform.

Variants with clinical analogy to the scarring mucous membrane pemphigoid show mucous membrane infestation of the oral mucosa, pharynx, nose, eyes.

Frequently herpetiform or rosette-like arranged, but also anular or garland-like configured, moderately to intensely itching, urticarial plaques with marginal vesicular or bullous lesions. The rosette shape is caused by the intermittent appearance of annular vesicular neoplasms around older, not yet healed blisters.

In individual cases the picture of bullous dermatosis can be supplemented by IgA-purpura (Purpura Schönlein-Henoch).

Remark: The clinical pictures correspond on the one hand to the dermatitis herpetiformis and on the other hand to the bullous pemphigoid. In rare cases there are also extensive skin manifestations reminiscent of the erythema exsudativum multiforme, also under the clinical presentation of Stevens-Johnson syndrome.

In 50% of patients there are mucosal changes, especially in the oral mucosa and conjunctiva;

less frequently associated: ulcerative colitis, Crohn's disease, IgA nephropathy or eosinophilic pneumonia.

• The histology of the LAD is not diagnostic!
• Both subepidermal blistering with infiltrate from lymphocytes and numerous neutrophil granulocytes and occasionally intrapapillary microabscesses are found, as well as subepidermal blistering with perivascular and interstitial lymphocytic infiltrate.
• Immunoelectron microscopically 2 types can be distinguished, the more common lamina lucida type and the sublamina densa type.

• Clinical signs: Bullous pemphigoid, pemphigoid, scarring (mucous membrane pemphigoid), dermatitis herpetiformis Duhring, epidermolysis bullosa acquisita, bullous impetigo, bullous drug exanthema, erythema exsudativum multiforme.
• Histological: Dermatitis herpetiformis Duhring, inflammatory epidermolysis bullosa acquisita, bullous pemphigoid, bullous drug exanthema.

Associated diseases were mostly described in individual cases:

• M. Crohn
• Gluten-sensitive enteropathy (0-24%)
• ulcerative colitis
• systemic lupus erythematosus
• Dermatomyositis
• Malignancies (B-cell lymphoma, myeloid leukaemia)

Antipruriginous and anti-inflammatory treatment e.g. with 3-5% polidocanol lotio(e.g. Optiderm, R200) alternating with weak to medium-strong glucocorticoids such as 1% hydrocortisone cream(e.g.hydrogals, R119 ), 0.1% hydrocortisone-17-butyrate cream (e.g. Laticort), 0.1% methylprednisolone cream (e.g. Advantan), 0.1% mometasone fat cream(e.g. Ecural). Treatment with synthetic tanning agents, e.g. Tannosynt, Tannolact, has also proven to be effective.

The first choice is DADPS (e.g. Dapson-Fatol). Gradual dosage, initially 50-75 mg/day, after 2 weeks full dose from 100-150 mg/day to max. 300 mg/day. Maintenance dose according to clinic (wide range of variation). Initially adjuvant prednisone (e.g. Decortin) 20-40 mg/day p.o. If the results improve, continue dapsone as monotherapy, if the results deteriorate, temporary adjuvant administration of prednisolone. At the earliest after 6 months of freedom from symptoms.

If the clinical success is unsatisfactory, the use of azathioprine (e.g. Imurek) 1-2 mg/kg bw/day in combination with systemic corticoids may be considered. Further treatment options are cyclophosphamide, mycophenolate mofetil, colchicine, methotrexate and ciclosporin A.

To reduce itching, additional systemic administration of antihistamines such as desloratadine (e.g. Aerius) 5 mg/day p.o. or levocetirizine (e.g. Xusal) 10 mg/day p.o. may be necessary.

Dietetic measures are largely ineffective in IgA linear dermatosis.

In idiopathic LAD, a course lasting for years must be expected.

In the case of LAD triggered by medication, healing can be expected within a few weeks/months after discontinuation of the triggering medication.

While the skin changes heal without scarring, eye involvement can lead to scarring, and in extreme cases to blindness.

The prognosis of the disease also depends on the organ involvement: ulcerative colitis, Crohn's disease, IgA nephropathy, gluten-sensitive enteropathy.

Linear IgA dermatosis, bullous pemphigoid, pemphigoid gestationis and mucous membrane pemphigoid have the identical target antigen (BP 180/type VIII collagen). In contrast to these, however, the autoantibody of linear IgA dermatosis belongs to the IgA class.

The role of ulcerative colitis as rare concomitant disease of IgA linear dermatosis remains unclear so far. It can precede the LAD by years.

1. Allen J, Wojnarowska F (2003) Linear IgA disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD 285 and a dermal 180-kDa protein. Br J Dermatol 149: 1055-1058
2. Avci O et al (2003) Acetaminophen-induced linear IgA bullous dermatosis. J Am Acad Dermatol 48: 299-301
3. Chorzelski TP, Jablonska S (1975) Diagnostic significance of immunofluorescent pattern in dermatitis herpetiformis. Int J Dermatol 14: 429-436
4. Chorzelski TP, Jablonska S (1979) IgA linear dermatosis of childhood. Br J Dermatol 101: 535-542
5. Choudhry SZ et al (2015) Vancomycin-induced linear IgA bullous dermatosis demonstrating the isomorphic phenomenon. Int J Dermatol 54:1211-1213
6. Georgi M et al (2001) Autoantigens of subepidermal bullous autoimmune dermatoses. dermatologist 52: 1079-1089
7. Hollo P et al (2003) Linear IgA dermatosis associated with chronic clonal myeloproliferative disease. Int J Dermatol 42: 143-146
8. Kim JS et al (2015) Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy. Ann Dermatol 27:315-318
9. Klein A et al (2010) Linear IgA dermatosis with eye involvement in association with ulcerative colitis. Dermatologist 61:55-57
10. Lings K et al (2015) Linear IgA bullous dermatosis: a retrospective study of 23 patients in Denmark. Acta Derm Venereol 95: 466-471
11. Palmer RA et al (2001) Vancomycin-induced linear IgA disease with autoantibodies to BP180 and LAD285. Br J Dermatol 145: 816-820
12. Pena-Penabad C et al (2003) Linear IgA bullous dermatosis induced by angiotensin receptor antagonists. At J Med 114: 163-164
13. Romani L et al (2015) A Case of Neonatal Linear IgA Bullous Dermatosis with Severe Eye Involvement. Acta Derm Venereol 95:1015-1017
14. Zone JJ (2001) Clinical spectrum, pathogenesis and treatment of linear IgA bullous dermatosis. J Dermatol 28: 651-653