Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. OBJECTIVES: To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. METHODS: This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. RESULTS: Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. CONCLUSIONS: Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution.

Oral cyclophosphamide without corticosteroids to treat mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. Immunosuppressants, such as cyclophosphamide (CYC), are indicated for patients with severe and/or refractory MMP. OBJECTIVES: To evaluate the efficacy and safety of daily oral CYC without corticosteroids as therapy for severe MMP. METHODS: Thirteen patients with severe refractory MMP, who received oral CYC at an initial dose of 2 mg kg(-1) without corticosteroids, were retained. Previous treatments, for example dapsone, sulfasalazine or topical agents, were maintained during CYC treatment. Initial clinical severity and response to treatment were assessed by scoring. CYC was stopped after complete remission (CR), or when MMP progressed or lymphopenia (< 0·7 × 10(9) cells L(-1) ) occurred. RESULTS: After 52 weeks of CYC treatment, the overall response rate was 69% (9/13 patients) with a median time to disease control of 8 weeks (range 4-52 weeks). Seven patients (54%) entered CR with a median time to CR of 24 weeks (range 16-52 weeks), all remaining in CR at week 52. The mean duration of CYC administration was 12 weeks (range 2-52 weeks). The most common side effect was lymphopenia (10/13 patients), which led to CYC withdrawal for six patients. No sepsis was observed. CONCLUSIONS: CYC without corticosteroids had rapid efficacy in patients with severe refractory MMP and was safe.

Place of human amniotic membrane immunoblotting in the diagnosis of autoimmune bullous dermatoses.

BACKGROUND: Fine analysis of antiskin autoantibodies can contribute to the differential diagnosis of autoimmune bullous dermatoses. OBJECTIVES: To develop a high-performance immunoblotting method using human amniotic membrane as the antigen source, and to compare it with current laboratory methods. METHODS: Sera from 113 patients were tested by immunoblotting (IB), rat and monkey oesophagus and salt-split skin indirect immunofluorescence (IIF), and enzyme-linked immunosorbent assay (ELISA) quantification of anti-BP180-NC16a and anti-BP230, or antidesmoglein (Dsg) 1 and 3 antibodies. There were 56 cases of bullous pemphigoid (BP), 22 cases of mucous membrane pemphigoid (MMP), eight cases of epidermolysis bullosa acquisita (EBA), two cases of bullous systemic lupus erythematosus (BSLE), 17 cases of pemphigus vulgaris (PV), and four cases each of pemphigus foliaceus (PF) and paraneoplastic pemphigus (PNP). RESULTS: In BP, the three methods had similar sensitivity (84-89%) for both anti-BP180-NC16a and anti-BP230 antibody detection. In MMP, autoantibodies (mainly directed against BP180 or laminin 332 subunits) were detected in 77% of patients by IB, compared with only 9% by IIF on rat and monkey oesophagus and 36% on salt-split skin, and 14% by anti-BP180-NC16a and anti-BP230 ELISA. In patients with pemphigus, ELISA had 92% sensitivity for anti-Dsg1 and 3, but IB and rat bladder IIF were necessary to confirm PNP by revealing specific and rare patterns (antidesmoplakin I/II, antienvoplakin and antiperiplakin antibodies). IB also revealed anticollagen VII antibodies in 60% of patients with EBA and BSLE, and antibodies to BP180, BP230 and Dsg3 in a few patients who were negative using the other two techniques. CONCLUSION: Amniotic membrane immunoblotting is an interesting diagnostic tool for bullous diseases, as the entire panel of autoantibodies can be detected with a single extract. This method improves the identification of complex and heterogeneous autoimmune processes in conjunction with IIF and ELISA, and is particularly useful for MMP characterization.

Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren's syndrome.

BACKGROUND: B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases. OBJECTIVE: To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay. RESULTS: Mean (standard error (SE)) serum kappa and lambda FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4) mg/l, p<0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v 11.6 (0.6) mg/l, p<0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04 for lambda). CONCLUSION: FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases.

Prevalence of anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with primary Sjögren's syndrome.

OBJECTIVE: To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKA) in patients with primary Sjögren's syndrome. METHODS: 149 patients with a diagnosis of primary Sjögren's syndrome according to the European/American consensus criteria were recruited from three French medical centres. The presence of anti-CCP was determined by enzyme linked immunosorbent assay and of AKA antibodies by indirect immunofluorescence. Radiographs of hands and feet were evaluated at the time of anti-CCP analysis. RESULTS: Six patients with radiological erosions and nine patients with non-erosive arthritis fulfilling ACR criteria for rheumatoid arthritis were thought to have rheumatoid arthritis and secondary Sjögren's syndrome, while 134 were considered to have primary Sjögren's syndrome (mean (SD) disease duration, 11.1 (6.6) years). Of these, 80 tested positive for IgM rheumatoid factor (RF) (59%), 10 (7.5%) for anti-CCP, 7 (5.2%) for AKA, and 5 (3.7%) for both anti-CCP and AKA. There was no difference in clinical and biological features, including prevalence of RF, between anti-CCP positive and negative patients. The nine Sjögren patients with non-erosive arthritis, fulfilling ACR criteria for rheumatoid arthritis, were all CCP positive. Their response to disease modifying antirheumatic drugs could be different from classical rheumatoid patients. CONCLUSIONS: Most patients with primary Sjögren's syndrome are negative for AKA and anti-CCP, but positive test results should not rule out this diagnosis. Anti-CCP positive patients, who may be prone to developing rheumatoid arthritis, require cautious clinical and radiographic follow up.