This is also known as Linear IgA bullous dermatosis (LABD). It present with two variants. The childhood variant is known as chronic bullous dermatosis of childhood or juvenile dermatitis herpetiformis. It arises within the first decade of life with large, tense bullae on an erythematous base and cocurs on the perioral, genital skin, lower abdomen and thighs. There is a characteristic grouping called a cluster of jewels with polycyclic grouping. Although benign, the lesions may persist for several months or years and may rarely persist to puberty. If there is severe scarring, the term childhood cicatricial pemphigoid has been used. There may be an association with HLA antigen B8.
The adult variant is characterized by lesions resembling dermatitis herpetiformis and bullous pemphigoid. These usually annular lesions involve the trunk, limbs, oral mucosa, and conjunctiva. Facial and perineal involvement are uncommon. Pruritis and burning may be present. This is a chronic disorder and lesions may persist indefinitely. There is a lesser association with HLA B8.
Both variants arise from the binding of IgA to two dermal antigens. The first is a LAD-1, a 97 kd protein within the anchoring filament protein ladinin. The second is a 290 kd antigen in type VII collagen. These circulating autoantibodies are found in 70% of childhood cases and 20% of adult cases. Unlike dermatitis herpetiformis, there are no circulating antiendomysial antibodies nor is there a gluten sensitive enteropathy. There is an association with other autoimmune disorders and various drugs which all cause flares usually occurring within 4-14 days following ingestion. This drug associated variant may be the most common form of the disease.
This is a subepidermal blistering disease with histologic features indistinguishable from dermatitis herpetiformis. Thus direct immunofluorescence (DIF) is needed to confirm the diagnosis. Dermal papillary microabscesses are present leading the subepidermal cleft and blister formation. DIF reveals a linear staining for IgA at the dermoepidermal junction. In 20% of cases, there is also IgG, IgM, and C3.
As mentioned, distinction from dermatitis herpetiformis is necessary. IgA is also deposited along the basement of eccrine secretory coils in patients with alcoholic liver disease, a potential false positive.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
Linear IgA bullous dermatosis of childhood: a long-term study.
Kulthanan K, Akaraphanth R, Piamphongsant T, Kullavanijaya P.
Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
J Med Assoc Thai 1999 Jul;82(7):707-12 Abstract quote
BACKGROUND: Linear IgA bullous dermatosis (LAD) of childhood is a rare acquired subepidermal blistering disease of young children. Most of the studies were reported from the USA and European countries.
METHOD: Twelve cases of Thai patients diagnosed as LAD of childhood were analyzed concerning clinical, histopathological, immunopathological findings including treatment responses and courses compared with those of Caucasians.
RESULT: The mean age of onset was 5.1 years. The areas of common involvement were the perioral region, lower abdomen, perineum, buttock, inner thighs and extremities. Histopathology in half of the cases showed features of dermatitis herpetiformis or bullous pemphigoid. All patients had positive linear IgA band at the basement membrane zone (BMZ) by direct immunofluorescence. Only one patient had positive circulating anti BMZ antibody at the titer of 1:10. Most patients responded well to dapsone. The mean duration before remission was 1.9 years.
CONCLUSION: Our study in Thai patients with LAD of childhood produced data similar to previous studies carried out in the Caucasian nations.
DISEASE ASSOCIATIONS CHARACTERIZATION AUTOIMMUNE DISEASE Ulcerative colitis and rheumatoid arthritis CASTLEMAN'S DISEASE
Linear IgA disease in a patient with Castleman's disease.
Muncaster A, Lewis HM.
Department of Dermatology, Selly Oak Hospital, University Hospital Birmingham NHS Trust, Birmingham.
Clin Exp Dermatol 2002 Jan;27(1):24-6 Abstract quote
Linear IgA disease (LAD) is a well recognized subepidermal blistering disorder characterized by linear deposits of IgA at the basement membrane zone. The aetiology is unknown but there is a recognized association with lymphoproliferative malignancies.
We report a case of LAD occurring in a patient with multicentric Castleman's disease (angiofollicular lymph node hyperplasia), an association not previously recorded in the literature.
Br J Dermatol. 2005 Nov;153(5):1050-2. Abstract quote
Linear IgA disease has been reported in association with inflammatory bowel disease, in particular ulcerative colitis.
We experienced a case of linear IgA disease that occurred simultaneously with colonic Crohn's disease in a 55-year-old woman and rather unusually both skin and bowel disease improved in tandem.
We report the presentation, investigations and subsequent improvement of our patient and speculate on possible causes.
Vancomycin (About 50% of all cases)
- A morbilliform variant of vancomycin-induced linear IgA bullous dermatosis.
Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
- Arch Dermatol. 2008 Jun;144(6):774-8. Abstract quote
BACKGROUND: Linear IgA bullous dermatosis is an autoimmune blistering disease characterized clinically by the presence of small tense blisters and immunologically by the presence of IgA at the dermal-epidermal junction. Idiopathic, systemic disease-related, and drug-related versions of this disorder have been described, with the latter most commonly associated with vancomycin.
OBSERVATIONS: We describe 2 patients with vancomycin-associated linear IgA bullous dermatosis who presented with a morbilliform eruption that lacked blistering. Lesional and perilesional tissue from each patient was examined by light microscopy and direct immunofluorescence. Histopathologic examination findings revealed vacuolar interface dermatitis with a mixed inflammatory infiltrate and occasional eosinophils, consistent with a drug eruption. Direct immunofluorescence revealed IgA deposited in a linear pattern at the dermoepidermal junction. In both patients, the results of indirect immunofluorescence using both IgG and IgA were negative.
CONCLUSIONS: These cases highlight the existence of a new form of linear IgA bullous dermatosis presenting as a morbilliform drug eruption. Both patients were following extensive medication regimens, including use of multiple antibiotics. The diagnosis of linear IgA bullous dermatosis allowed us to target vancomycin as the likely allergen and begin treatment. In light of these findings, direct immunofluorescence may be a useful diagnostic adjunct in determining the cause of drug eruptions.
J Dermatol. 2005 Sep;32(9):759-64. Abstract quote
We report the case of a 69-year-old Japanese woman with multiple blistering lesions covering almost her whole body. Linear IgA and C3 depositions were seen at the basement membrane zone on direct immunofluorescence (IF). Linear IgA bullous dermatosis (LABD) is one of the autoimmune diseases resulting in subepidermal blisters.
It is clinically similar to bullous pemphigoid and IF is required to distinguish the two diseases. In this case, the blistering lesions appeared after vancomycin treatment. This drug was strongly suspected as a cause of LABD in light of the clinical course of the patient even though a drug-lymphocyte stimulating test was negative.
Among the various implicated causative drugs, vancomycin is the most commonly associated with LABD.
Vancomycin-induced linear IgA disease manifesting as bullous erythema multiforme.
Armstrong AW, Fazeli A, Yeh SW, Mackool BT, Liu V.
Harvard Medical School, Pasteur/Doris Duke Clinical Research Fellowship, Boston, MA, USA.
J Cutan Pathol. 2004 May;31(5):393-7. Abstract quote
Background: Vancomycin-induced linear immunoglobulin A (IgA) disease, an autoimmune, blistering disease in response to vancomycin administration, is characterized by a subepidermal, vesiculobullous eruption and linear IgA deposition along the basement membrane zone on direct immunofluorescence.
Case report: We report the case of an 81-year-old man treated with vancomycin who developed diffuse erythema multiforme and tense bullae involving the palmoplantar surfaces. Discontinuation of vancomycin therapy resulted in complete resolution of this patient's cutaneous eruption.
Results: Biopsy of a representative skin lesion demonstrated lichenoid interface dermatitis with focal subepidermal clefting, dyskeratosis, and prominent eosinophils. Direct immunofluorescence showed linear basement membrane staining with immunoreactants to IgA; indirect immunofluorescence demonstrated the presence of circulating IgG antibodies binding in an intercellular pattern. Immunoprecipitation studies using the patient's serum revealed 210, 130, and 83 kDa target antigens.
Conclusions: Presenting with an initial clinical picture suggestive of bullous erythema multiforme, this patient's subsequent clinical course and direct immunofluorescence confirm the diagnosis of linear IgA bullous disease (LABD). His indirect immunofluorescence findings and immunoprecipitation results suggest that circulating non-IgA antibodies may represent a newly recognized immunopathologic feature of vancomycin-induced linear IgA disease, underscoring the variable and unpredictable manifestations of this drug-induced cutaneous disease.
Vancomycin-induced linear IgA bullous dermatosis (LABD).
Whitworth JM, Thomas I, Peltz SA, Sullivan BC, Wolf AH, Cytryn AS.
Dermatology Service, University of Medicine and Dentistry of New Jersey, Newark, USA.
J Am Acad Dermatol 1996 May;34(5 Pt 2):890-1 Abstract quote
We report the eleventh case of vancomycin-induced linear IgA disease. Our case is unusual because symptoms developed within minutes of administration of the drug.
We discuss the pathogenesis and review the literature.
Drug-induced linear IgA bullous disease following antibiotics.
Wiadrowski TP, Reid CM.
Flinders Medical Centre, Bedford Park and Royal Adelaide Hospital, Adelaide, South Australia, Australia
Australas J Dermatol 2001 Aug;42(3):196-9 Abstract quote
A 69-year-old woman presented with pneumonia and subacute bacterial endocarditis. Nine days after intravenous vancomycin and ciprofloxacin were commenced, the patient developed a bullous mucocutaneous eruption.
Clinical presentation and histopathology were consistent with drug-induced linear IgA bullous disease (LABD). The patient's lesions resolved with cessation of antibiotics.
A review of the features of drug-induced LABD and the drugs that have been implicated are presented.
Linear IgA bullous dermatosis induced by atorvastatin
Cathrin König, etal.
J Am Acad Dermatol 2001;44:689-92 Abstract quote
Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disease characterized by circulating IgA antibodies binding the basement membrane zone. In most cases the origin is not clear, but in a minority of cases LABD is drug induced.
We describe a patient in whom linear IgA disease developed shortly after beginning therapy with atorvastatin. In Western blotting analysis we detected IgA and IgG class antibodies targeting a 97-kd protein.
To our knowledge this is the first reported case of atorvastatin-induced LABD.
Linear IgA bullous dermatosis in one of two piroxicam-induced eruptions: A distinct direct immunofluorescence trend revealed by the literature
Richard W. Plunkett, PhD
Stephen E. Chiarello, MD
Ernst H. Beutner, PhD
Buffalo, New York, and Port Charlotte, Florida
J Am Acad Dermatol 2001;45:691-6. Abstract quote
Background: The report focuses first on two patients with piroxicam-induced bullous eruption, one whose disease was diagnosed as linear IgA bullous dermatosis (LABD) and the other with no disease-specific immunologic findings using immunofluorescence methods. A review of the literature points to a distinctive direct immunofluorescence feature of drug-induced LABD cases.
Objective: Our purposes were to focus on divergent piroxicam reactions and to compare immunofluorescence findings in our and other reported drug-induced LABD cases to randomly occurring LABD cases.
Methods: Direct and indirect immunofluorescence methods were used to study biopsy and serum samples from both cases and biopsy specimens of 40 other LABD cases.
Results: Tense blisters developed in two patients medicated with piroxicam. Immunofluorescence studies demonstrated deposits of IgA at the basement membrane zone (BMZ) in case 1 and only non-disease-specific fibrin deposits at the BMZ in case 2. Within 1 month of discontinuation of piroxicam, all lesions were gone in both patients.
Conclusion: In LABD cases proven by direct immunofluorescence, (1) the index of suspicion of drug induction should be higher in cases with only IgA and no IgG in the BMZ; (2) possibly up to two thirds of all LABD cases may be drug induced; and (3) the negative immunofluorescence findings in case 2 and other cases reported in the literature suggest that LABD is one of several host responses in drug-induced blistering diseases.
Linear IgA dermatosis and Hodgkin's lymphoma--report of a case in an African and review of the literature.
Jacyk WK, Nagel GJ, van der Hoven AE.
Department of Dermatology, Kalafong Hospital, Pretoria, Republic of South Africa
J Dermatol 1990 Oct;17(10):633-7 Abstract quote
Linear IgA dermatosis and Hodgkin's lymphoma were diagnosed at the same time in a 47-year-old Black South African man. Skin changes of linear IgA dermatosis responded to a combined treatment with dapsone and MOPP regimen. Prior administration of dapsone alone did not result in improvement of the skin condition.
Four documented cases of linear IgA dermatosis and lymphoma outside the gastrointestinal tract, three of them of Hodgkin's type, have been reported in the literature. Review of the literature suggests that different forms of lymphoma seem to be associated with linear IgA dermatosis and dermatitis herpetiformis.
The present patient represents the first immunologically verified case of linear IgA dermatosis in an adult Black African.
Linear IgA disease and pregnancy.
Collier PM, Kelly SE, Wojnarowska F.
Department of Dermatology, Bristol Royal Infirmary, United Kingdom.
J Am Acad Dermatol 1994 Mar;30(3):407-11 Abstract quote
BACKGROUND: Although many patients with linear IgA dermatosis (LAD) are young and have persistent disease, little is known about the interactions between LAD and pregnancy.
OBJECTIVE: Our purpose was to study the effects of LAD on pregnancy, and vice versa.
METHODS: Our study included 12 patients with LAD who underwent a total of 19 pregnancies.
RESULTS: In all patients the disease improved during pregnancy, enabling therapy to be reduced or stopped. Dapsone was taken by patients during 11 pregnancies, and no adverse effects were seen. No patients had problems in labor. Most patients had a relapse approximately 3 months post partum, even if they had previously been in remission. In two patients, disease started within 3 months of delivery. Fetal outcome was unaffected in all but one fetus, who had a single transient blister.
CONCLUSION: We found no contraindication to pregnancy in patients with LAD. We recommend that therapy be reduced or stopped whenever possible during pregnancy and that patients be counseled about the possibility of a relapse post partum.
Linear IgA disease and ulcerative colitis.
De Simone C, Guerriero C, Pellicano R.
Department of Dermatology Universita Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168 Roma, Italy.
Eur J Dermatol 1998 Jan-Feb;8(1):48-50 Abstract quote
Linear IgA disease is an acquired bullous disease of the skin characterized by linear IgA deposits along the dermal-epidermal junction. Inflammatory bowel diseases have been rarely reported in association with linear IgA disease.
We have recently observed a patient suffering from ulcerative colitis who developed a cutaneous bullous eruption that was diagnosed as a linear IgA disease. Foreign antigens penetrating the inflamed bowel mucosa might give rise to the production of autoantibodies cross-reacting with the cutaneous antigens involved in the pathogenesis of linear IgA disease.
PATHOGENESIS CHARACTERIZATION Autoantibodies 97kDa
Present in both childhood and adult forms
230 kDa and 180 kDa
Clin Exp Dermatol. 2005 Nov;30(6):682-7. Abstract quote
Collagen XVII, or BP180, is a collagenous transmembrane protein and a structural component of the dermoepidermal anchoring complex. Molecular studies reveal that it has a globular cytosolic amino-terminal domain and flexible-rod extracellular carboxyterminal domain. The extracellular portion of collagen XVII is constitutively shed from the cell surface by ADAMs (proteinases that contain adhesive and metalloprotease domains). Cell biological analyses suggest that collagen XVII functions as a cell-matrix adhesion molecule through stabilization of the hemidesmosome complex.
This concept is supported by investigations into human diseases of the dermoepidermal junction, in which collagen XVII is either genetically defective or absent (as in some forms of nonlethal junctional epidermolysis bullosa). Autoantibodies against collagen XVII (BP180) are seen in bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, linear IgA disease, lichen planus pemphigoides and pemphigoid nodularis. In vivo and in vitro studies provide evidence for a pathogenic role of these autoantibodies, and suggest that the serum level and epitope specificity of these antibodies influences disease severity and phenotype.
This review summarizes the structural and biological features of collagen XVII and its role in diseases of the basement membrane zone.
Mapping of epitopes on the BP180 ectodomain targeted by IgA and IgG autoantibodies in patients with the lamina lucida-type of linear IgA disease.
Georgi M, Scheckenbach C, Kromminga A, Partscht K, Messer G, Brocker EB, Zillikens D.
Department of Dermatology, University of Wurzburg, Josef-Schneider-Str. 2, 97080 Wurzburg, Germany.
Arch Dermatol Res 2001 Mar;293(3):109-14 Abstract quote
Linear IgA disease (LAD) is an autoimmune subepidermal blistering skin disease characterized by the linear deposition of IgA at the dermoepidermal junction.
Serum from patients with LAD most commonly contains autoantibodies that are directed against the hemidesmosomal transmembrane glycoprotein BP180 (type XVII collagen). Various antigenic sites on the extracellular domain of this anchoring filament protein have been shown to be targeted by autoantibodies in different autoimmune bullous skin diseases, including bullous pemphigoid and cicatricial pemphigoid (CP).
However, little is known about epitopes on BP180 recognized by autoantibodies in LAD. In this study, we used three recombinant GST fusion proteins, together roughly covering the entire BP180 ectodomain, to characterize the autoimmune response in serum from patients with LAD. Interestingly, we found both IgA and IgG reactivity to all three portions of the BP180 ectodomain. The strongest reactivity was observed with the C-terminal portion of BP180. This is also the major region recognized by autoantibodies in patients with CP.
This finding correlates with the observation that there may be significant overlap of the clinical and immunopathological findings in LAD and CP.
Autoimmune responses in patients with linear IgA bullous dermatosis: both autoantibodies and T lymphocytes recognize the NC16A domain of the BP180 molecule.
Lin MS, Fu CL, Olague-Marchan M, Hacker MK, Zillikens D, Giudice GJ, Fairley JA.
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Clin Immunol 2002 Mar;102(3):310-9 Abstract quote
Linear IgA bullous disease (LABD) is an autoimmune skin disease characterized by subepidermal blisters and IgA autoantibodies directed against the epidermal basement membrane zone (BMZ) of the skin.
Various antigens have been identified as targets of IgA autoantibodies including BP180, a type II glycoprotein that spans the BMZ and lamina lucida. Previously, we have identified a subset of LABD patients whose sera contained IgA antibodies against the 16th noncollagenous (NC16A) domain of BP180. NC16A was previously shown to harbor epitopes that are recognized by both autoantibodies and T cells from patients with bullous pemphigoid and herpes gestationis and is thought to be associated with the development of these immunobullous diseases.
The aim of this study was to determine whether T lymphocytes from LABD patients with anti-NC16A IgA autoantibodies respond to epitopes in the same region of the BP180 protein. Indeed, of the four LABD patients in our study, all had T cells that specifically proliferated in response to NC16A. Moreover, two subfragments of NC16A were identified as the predominant targets of LABD T cells. Further analysis of T cell lines and clones derived from these patients revealed that these cells express a CD4 memory T cell phenotype and secrete a Th1/Th2 mixed-cytokine profile, characteristics similar to those of T cells in bullous pemphigoid patients.
Our data suggest that the BP180 protein, typically the NC16A region, is the common target of both cellular and humoral immune responses in some LABD patients. This information helps to further elucidate the autoimmune mechanisms in this disease.
CLINICAL VARIANTS CHARACTERIZATION GENERAL
Linear IgA disease in adults.
Leonard JN, Haffenden GP, Ring NP, McMinn RM, Sidgwick A, Mowbray JF, Unsworth DJ, Holborow EJ, Blenkinsopp WK, Swain AF, Fry L.
Br J Dermatol 1982 Sep;107(3):301-16 Abstract quote
A multi-centre study is described in which thirty-five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty-two patients with linear IgA deposits, of whom thirty-four had homogeneous-linear (HL) and eight had granular-linear (GL) IgA deposits.
The three groups were similar with regard to age of onset, presence of circulating immune complexes and auto-antibodies, incidence of spontaneous remission, histology of lesional skin and response to dapsone. There was a female predominance in the HL group in contrast to the male predominance in the other two. It was not possible to diagnose the HL group clinically. Some patients had a rash typical of DH whilst others resembled pemphigoid. In the majority, however, no specific diagnosis could be made with confidence. The GL group clinically resembled the DH group. The incidence of positive potassium iodide patch tests was greater in the DH group than in the other two. An associated enteropathy was found in 24% of patients in the HL group, 30% of patients in the GL group and 85% of patients in the DH group. Fifty-six percent of HL patients had HLA-B8 compared with 50% in the GL group and 88% in the DH group.
Patients with linear IgA deposits may not be a uniform group, but until they can be divided into specific subgroups (e.g. by ultrastructural localization of the deposit or by response to a gluten-free diet) we propose that the term adult linear IgA diseases should be used to distinguish these patients from those with papillary IgA deposits.
Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap.
Wojnarowska F, Marsden RA, Bhogal B, Black MM.
Department of Dermatology, Slade Hospital, Oxford, England.
J Am Acad Dermatol 1988 Nov;19(5 Pt 1):792-805 Abstract quote
Linear IgA disease of adults, chronic bullous disease of childhood, and the rare childhood cicatricial pemphigoid currently are regarded as separate clinical entities despite their many shared features. All are sulfone-responsive subepidermal bullous diseases associated with linear IgA deposition at the basement membrane zone.
In this paper we present a long-term study of 25 cases of adult linear IgA disease, 25 cases of chronic bullous disease of childhood, and four cases of childhood cicatricial pemphigoid, which has revealed further similarities among all three groups. The morphology and distribution of the cutaneous and mucosal lesions were similar; mucosal involvement was present in 80% of patients with adult linear IgA disease, 64% of those with chronic bullous disease of childhood, and 100% of those with childhood cicatricial pemphigoid, and ocular scarring affected patients in all groups.
Remission occurred in 64% of those with chronic bullous disease of childhood (the disease was active in 12% after puberty), 48% of those with adult linear IgA disease, and in no cases of childhood cicatricial pemphigoid. HLA B8 and circulating IgA anti-basement membrane zone antibody were more common in chronic bullous disease of childhood than adult linear IgA disease.
There were no absolute differences among the three groups, and we suggest that adult linear IgA disease, chronic bullous disease of childhood, and childhood cicatricial pemphigoid are the same disease, with childhood cicatricial pemphigoid being a more severe form of chronic bullous disease of childhood.
Benign chronic bullous dermatosis of childhood: a review.
Sweren RJ, Burnett JW.
Cutis 1982 Apr;29(4):350-2, 356-7 Abstract quote
Chronic bullous dermatosis of childhood is one of the nonhereditary blistering diseases of children. Clinically, it is characterized by predominantly monomorphous, large tense bullae, which often form a "rosette pattern" or "jewel-like" clustering and have a predilection for the lower trunk, pelvic region, and lower extremities.
Histologically, a subepidermal blister is seen, which is indistinguishable from either bullous pemphigoid or dermatitis herpetiformis. Although usually responsive to sulfone therapy, some cases require the combination of sulfones and systemic corticosteroids or corticosteroids alone to control the disease.
Recent advances in immunologic techniques reveal: 1. a linear band of IgA at the dermal-epidermal junction on direct immunofluorescence that has been reported both in the lamina lucida and below the basal lamina on immunoelectron microscopy; 2. IgA antibasement membrane antibodies on indirect immunofluorescence; 3. normal jejunal biopsies; and 4. a high association with HLA-B8. It remains unclear whether chronic bullous dermatosis of childhood represents a separate disease entity or is merely a variant of dermatitis herpetiformis.
Chronic bullous dermatosis of childhood also differs from linear IgA dermatosis of the adult in that the latter is not associated with HLA-B8, and thus should not be confused with this disease by similar nomenclature.
IgA linear dermatosis of childhood (chronic bullous disease of childhood).
Chorzelski TP, Jablonska S.
Br J Dermatol 1979 Nov;101(5):535-42 Abstract quote
Of twenty-seven cases of subepidermal blistering disease of children twelve corresponded clinically, histologically and immunologically to dermatitis herpetiforms of adults, six to bullous pemphigoid, and eight to chronic bullous disease of childhood (CBDC), i.e. IgA linear dermatosis.
This latter disease seems to be a distinct entity, different from both dermatitis herpetiformis and bullous pemphigoid, and is characterized immunopathologically by linear IgA deposits at the basement membrane zone. These cases usually do not show intestinal involvement and respond well to combined treatment with sulphones and corticosteroids, whereas sulphones or sulphapyridine alone are, even in very high doses, not sufficient for full control of the disease.
CBDC or IgA linear dermatosis of childhood may be regarded as a counterpart of IgA linear dermatosis of adults.
Linear IgA dermatosis presenting with erythema annulare centrifugum lesions: report of three cases in adults.
Dippel E, Orfanos CE, Zouboulis C.
Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Germany.
J Eur Acad Dermatol Venereol 2000 Mar;15(2):167-70 Abstract quote
Linear IgA dermatosis presented with erythema annulare centrifugum lesions in three elderly women. Search for underlying malignancy revealed low-grade B-cell lymphoma in one case. In addition to subepidermal blistering, histology showed a typical mixed infiltrate of granulocytes and eosinophils and, occasionally, papillar microabsesses in one case. In the two other subjects, characteristic subepidermal lining with granulocytes was observed. Immunofluorescence studies confirmed the diagnosis, while autoantibodies characteristic for dermatitis herpetiformis were absent.
To our knowledge this is the second report of adult linear IgA dermatosis in association with erythema annulare centrifugum lesions. Our observations concord with several other reports of figurate erythema associated with autoimmune blistering disease and other immune disorders.
Common antibody-related immunological mechanisms indicate that the two distinct clinical pictures are probably stages of the same pathogenic entity.
J Laryngol Otol. 2005 Apr;119(4):314-8. Abstract quote
Two cases of linear IgA bullous dermatosis initially presenting as ulcerative lesions in the larynx and pharynx are reported. It was difficult to diagnose and treat the lesions, but they were finally diagnosed from the histopathological findings of accompanying skin lesion specimens.
One of the patients required a tracheostomy due to increased airway stenosis by a laryngeal lesion. Despite general corticosteroid administration this could not be completely resolved, although partial opening of the glottis was observed, and the patient died of accidental tracheostomy tube complications during home care.
Although there are no reports of this disease in the otolaryngological field, these rare diseases involving the skin and entire body should be considered in the differential diagnosis of laryngeal and pharyngeal ulcerative lesions, including airway stenosis.
Furthermore, simple and safe procedures for relieving airway stenosis should be selected for rare and difficult-to-diagnose airway disease, prior to the final diagnosis.
Oral manifestations of linear IgA disease.
Chan LS, Regezi JA, Cooper KD.
Department of Dermatology, University of Michigan Medical Center, Ann Arbor
J Am Acad Dermatol 1990 Feb;22(2 Pt 2):362-5 Abstract quote
A case of linear IgA disease with prominent oral lesions is presented. Oral manifestations in linear IgA disease have been reported as minor clinical presentations.
In our patient the oral manifestations predominated and were the only clinical manifestations for 5 years before the skin lesions appeared. Linear IgA disease should be included in the differential diagnosis of bullous dermatoses with oral lesions.
Linear IgA disease manifesting as recalcitrant desquamative gingivitis.
Porter SR, Bain SE, Scully CM.
University Department of Oral Medicine, Surgery, and Pathology, Bristol Dental Hospital and School, England.
Oral Surg Oral Med Oral Pathol 1992 Aug;74(2):179-82 Abstract quote
A case of desquamative gingivitis caused by adult linear IgA disease is presented. Management initially proved to be difficult, however, the introduction of sulfapyridine caused rapid resolution of the gingival problem.
This is one of the first reports of desquamative gingivitis caused by linear IgA disease successfully treated with sulfapyridine.
HISTOLOGICAL TYPES CHARACTERIZATION SKIN Subepidermal or subepithelial bullous dermatosis
Collections of neutrophils, usually around the base of rete ridges
CHARACTERIZATION Direct immunofluorescence of skin (DIF) and salt split skin
Biopsy should be taken from perilesional skin or mucosa with normal and edge of lesional areas
If DIF is consistent with LABD, do salt split skin test to differentiate from epidermolysis bullosa form of LABD
Idiopathic 50% have basement membrane deposits of both IgA and IgG Drug Induced 89% have IgA but no IgG deposits at the basement membrane zone LABD variant of epidermolysis bullosa acquisita Antibodies to type VII collagen and laminin
An analysis of 24 patients with IgA deposition at the BMZ.
Weng MW, Qiu BS, Kang KF.
Institute of Dermatology, Shanghai Medical University, P.R. of China.
J Dermatol 1993 May;20(5):276-8 Abstract quote
A study of 24 patients with IgA deposition at the BMZ of the skin showed that five conditions could be recognized: 1) linear IgA bullous dermatosis in adults (LAD, 7 cases); 2) linear IgA and IgG bullous dermatosis in adults (LAGD, 10 cases); 3) chronic bullous disease of childhood (CBDC, 3 cases); 4) dermatitis herpetiformis (DH, 1 case), and 5) systemic lupus erythematosus (SLE, 3 cases).
Histopathologically, 5 of 7 patients with LAD were similar to the DH group, but 7 of 10 patients with LAGD were similar to the BP group. Half the patients with LAD and LAGD had oral lesions, and most of them had excellent responses to dapsone and Tripterygium Wilfordii, but the patients with CBDC did not respond to these treatments.
In the patients with LAD and LAGD, the positivity rates of IgA anti-BMZ antibodies examined by indirect immunofluorescence (IIF) on intact skin and NaCl split skin were 41% and 64%, respectively. The heterogeneity of the histopathologic pictures of LAD and LAGD, the incidence of DH, and the value of using NaCl split skin for IIF are discussed.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Other subepidermal blistering diseases, especially epidermolysis bullosa acquisita Antibodies positive for type VII collagen and laminin
Linear IgA disease with clinical and immunopathological features of epidermolysis bullosa acquisita.
Mutasim DF, Cummings MP.
Department of Dermatology, University of Cincinnati, Ohio 45267-0523, USA.
Pediatr Dermatol 1997 Jul-Aug;14(4):303-6 Abstract quote
A 10-year-old boy had a 3-month history of urticarial plaques and vesicles. Histologic and immunofluorescence testing confirmed the diagnosis of linear IgA disease.
Immunoelectron microscopy revealed IgA deposits in the sublamina densa area similar to those seen in epidermolysis bullosa acquisita. Milia developed after resolution of the lesions, similar to lesions of epidermolysis bullosa acquisita.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Epidermolysis bullosa acquisita form may be difficult to treat TREATMENT Idiopathic form may be more difficult to treat than drug induced form
Usually use dapsone and prednisone
J Am Acad Dermatol. 2006 Apr;54(4):652-6. Abstract quote
BACKGROUND: Linear IgA bullous dermatosis of childhood is a rare autoimmune bullous disease that mainly affects preschool-aged children. Dapsone is considered the first-line therapy with prompt response from most patients. However, it may be contraindicated in certain conditions such as glucose-6-phosphate dehydrogenase deficiency.
OBJECTIVE: We sought to assess the efficacy of flucloxacillin in the treatment of linear IgA bullous dermatosis.
METHODS: This is an observational study in which all confirmed cases of linear IgA bullous dermatosis (by both histological and immunofluorescence studies) will be treated with flucloxacillin. Flucloxacillin will be continued according to the response or otherwise will be discontinued after 8 weeks in the case of resistance.
RESULTS: We describe 7 patients with linear IgA bullous dermatosis of childhood treated with flucloxacillin. In 4 cases, it induced complete remission within 3 to 4 months of starting therapy with no relapses. In the other 3 cases, it successfully controlled the disease but with prompt relapse on discontinuation of the treatment.
LIMITATIONS: This is a case series study with a small number of patients.
CONCLUSION: Flucloxacillin may be considered among the first alternative therapies for linear IgA bullous dermatosis of childhood. Further evaluation of the efficacy and safety of the long-term use is required.
GLUTEN FREE DIET
Experience with a gluten free diet in the treatment of linear IgA disease.
Leonard JN, Griffiths CE, Powles AV, Haffenden GP, Fry L.
Acta Derm Venereol 1987;67(2):145-8 Abstract quote
A study was undertaken to determine whether the skin eruption of linear IgA disease (LAD) was gluten dependent.
Six patients with LAD were treated with a gluten free diet (GFD) for an average period of 33 months (range 19-48). Although one patient with LAD had an enteropathy which was clearly gluten sensitive, there was no convincing evidence that the rash of any of the patients responded to a GFD. Four of the six patients showed no significant alteration in their drug requirements. The remaining 2 patients showed a fall in minimum drug requirement but there was no increase after gluten challenge indicating that they were entering spontaneous remission.
This contrasts to the situation in dermatitis herpetiformis, where both the rash and the enteropathy are gluten dependent. These data add further to the evidence that LAD and dermatitis herpetiformis are separate entities.
Linear IgA bullous dermatosis responsive to a gluten-free diet.
Egan CA, Smith EP, Taylor TB, Meyer LJ, Samowitz WS, Zone JJ.
Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
Am J Gastroenterol 2001 Jun;96(6):1927-9 Abstract quote
Dermatitis herpetiformis is associated with a gluten-sensitive enteropathy in >85% of cases. Both the skin lesions and the enteropathy respond to gluten restriction. Linear IgA bullous dermatosis has a much lower prevalence of histological small bowel abnormalities, and lesions are not known to respond to gluten restriction.
We report a patient with linear IgA bullous dermatosis and gluten-sensitive enteropathy. This report addresses the issue of whether linear IgA bullous dermatosis can be associated with gluten-sensitive enteropathy. We evaluated the response to gluten restriction and normal diet by following the status of the patient's jejunal biopsies and skin lesions. The patient responded to gluten restriction, as shown by resolution of jejunal abnormalities and skin lesions and subsequently by recurrence of jejunal abnormalities and skin lesions with reinstitution of a gluten-containing diet.
This report demonstrates that linear IgA bullous dermatosis can respond to gluten restriction if an underlying gluten-sensitive enteropathy is present.
Linear IgA bullous disease limited to the eye: a diagnostic dilemma: response to intravenous immunoglobulin therapy.
Letko E, Bhol K, Foster CS, Ahmed AR.
The Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Uveitis and Immunology Service, Harvard Medical School, Boston, Massachusetts, USA.
Ophthalmology 2000 Aug;107(8):1524-8 Abstract quote
PURPOSE: To report on a diagnostic dilemma and treatment challenge in a patient with chronic cicatrizing conjunctivitis without involvement of skin and other mucous membranes persisting for 6 years and not responding to topical and systemic steroids.
DESIGN: Interventional case report.
METHODS: We performed direct immunofluorescence of the conjunctiva with fluorescein-conjugated rabbit antihuman antibodies against immunoglobulin A, G, and M, complement 3 component, and fibrinogen. To investigate the presence of circulating antibodies in patient's serum, indirect immunofluorescence using normal human conjunctiva, normal human skin, and monkey esophagus as substrate was done. In addition, we did immunoblot analysis using normal human epidermis as substrate to determine the molecular weight of an antigen. The patient was treated with intravenous immunoglobulin (IVIg). The correlation between the titer of circulating antibodies and the activity of conjunctival inflammation at various intervals during the course of IVIg therapy was demonstrated by immunoblot assay with serial dilutions of the patient's serum. The highest dilution at which the binding was visible was considered the titer.
RESULTS: Direct immunofluorescence of the conjunctiva and indirect immunofluorescence with both salt split skin and conjunctiva as substrate disclosed linear deposition of immunoglobulin A (IgA) at the epithelial basement membrane. Immunoblot analysis demonstrated the presence of IgA circulating antibodies in patient's serum directed against a 97kDa protein in human epidermis. A continuous decrease in the titer of these antibodies correlating to improvement of clinical symptoms was observed during IVIg therapy.
CONCLUSIONS: Use of a nonconventional diagnostic tool (immunoblot analysis), in addition to conventional immunohistologic studies, might be helpful in establishing the diagnosis of patients with chronic cicatrizing conjunctivitis. On the basis of results of these laboratory tests and clinical presentation, we believe that this patient has linear IgA bullous disease limited to the eye. IVIg therapy decreased the titer of circulating antibodies and induced a remission in this patient.
J Am Acad Dermatol 1994;30:35-357.
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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
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DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Collagen VII-Collagen variant present in the skin basement membrane within the anchoring fibrils.
Salt split skin assay-Normal skin incubated with 1M NaCl which separates the epidermis from dermis. The epidermal half contains the upper lamina lucida, hemidesmosomes, and BP antigen. The dermal half contains laminin 5, lamina densa, and anchoring fibrils.
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