Ziad Reguiai

Risk Factors for Relapse in Patients With Bullous Pemphigoid in Clinical Remission: A Multicenter, Prospective, Cohort Study

OBJECTIVE To identify prognostic factors for relapse in the first year after cessation of therapy in bullous pemphigoid (BP). DESIGN Prospective, multicenter, cohort study (January 1, 2000, through December 31, 2006). SETTING Fifteen French dermatology departments. Patients Patients with BP in remission under low doses of topical or systemic corticosteroids. Interventions Cessation of corticosteroid treatment (day 0) followed by a systematic clinical and immunologic follow-up. MAIN OUTCOME MEASURES The end point was clinical relapse within the first year after cessation of therapy. Associations of clinical, biological, and immunologic (including direct immunofluorescence, serum anti-basement membrane zone autoantibodies, and serum BP180 autoantibodies by enzyme-linked immunosorbent assay [ELISA] on day 0) variables with clinical relapse were assessed by means of univariate and multivariate analyses. RESULTS On day 0, 30 of 114 patients (26.3%) still had a positive result of direct immunofluorescence, 63 of 112 (56.3%) had circulating anti-basement membrane zone autoantibodies, and 34 of 57 (60%) had anti-BP180 antibodies by ELISA. At month 12, 22 patients were dead (n = 11) or lost to follow-up (n = 11), 51 were in remission, and 45 had had relapses (mean interval to relapse, 3.2 months). Factors predictive of relapse within 12 months after cessation of therapy were a positive result of direct immunofluorescence microscopy (P = .02), a greater age (P = .01), and high-titer ELISA scores (P = .02) on day 0. In multivariate analysis, the only factor independently predictive of relapse was a high-titer ELISA score on day 0 (odds ratio, 11.00; 95% confidence interval, 1.29-93.76). CONCLUSIONS High-titer anti-BP180 ELISA score and, to a lesser degree, a positive direct immunofluorescence finding are good indicators of further relapse of BP. At least 1 of these tests should be performed before therapy is discontinued.

Rituximab treatment of severe pemphigus: long-term results including immunologic follow-up.

BACKGROUND Rituximab (RTX) has been shown to be effective and safe for short-term treatment of severe pemphigus. Its long-term results remain unknown. OBJECTIVE We sought to evaluate long-term RTX efficacy and safety in comparison with classic immunosuppressants for the treatment of severe pemphigus. METHODS This retrospective study included, from 1997 to 2010, 24 consecutive patients with severe pemphigus, treated with RTX (n = 13) or systemic corticosteroids alone or combined with immunosuppressants (n = 11 control subjects). Anti-desmoglein antibodies were titered by enzyme-linked immunosorbent assay, every 3 months the first year, then at least annually. RESULTS Among the 13 patients treated with RTX, 9 achieved complete remission 3 months after a first RTX cycle. Thereafter, 7 patients (4 with maintenance therapy) relapsed within a mean of 18 months after the last RTX cycle and received 1 or 2 additional RTX cycles. With mean follow-up at 41 months after the first RTX cycle and 28 months after the last one, all 13 patients remained in complete remission (5 patients off therapy). No severe RTX side effects occurred. Anti-desmoglein-3 autoantibodies remained positive in 7 patients, despite long-term complete remission. Long-term remission rates and immunologic profiles did not differ between patients with pemphigus according to RTX status. LIMITATIONS This was a single-center, retrospective study. CONCLUSIONS RTX appeared to be an effective and well-tolerated treatment for severe pemphigus at long term. However, the long-term remission rate without maintenance therapy did not differ significantly from that of control subjects. Anti-desmoglein-1 autoantibody titers were more reliable than anti-desmoglein-3 titers for long-term follow-up.

Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy

BACKGROUND Calcinosis cutis (CC) encompasses debilitating complications of connective tissue disorders and chronic venous insufficiency. Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment for urolithiasis, pancreatolithiasis, and calcified tendinitis. This study prospectively evaluated ESWL efficacy and tolerance for patients with CC. METHODS This monocentric prospective study included all consecutive patients with CC progressing for at least 3 months, while their underlying causal disease was not. They underwent 3 ESWL sessions at 3-week intervals. The CC area and associated pain (visual analog scale score and analgesic consumption) were recorded before and 6 months after ESWL. RESULTS Eight patients were included: 4 with chronic venous insufficiency, 3 with systemic scleroderma, and one with dermatomyositis. ESWL was used to treat 10 CC lesions. Seven patients completed 3 ESWL sessions. Six months after ESWL, the median CC area had decreased from 3.1 to 1.9 cm(2). visual analog scale-assessed pain scores declined dramatically, from 7 to 2 of 10, as did analgesia consumption, without any difference according to the causal disease. LIMITATIONS Only 8 consecutive patients have been included and treated by ESWL during our study. CONCLUSION This evaluation of ESWL efficacy and tolerance for the treatment of CC found no difference between the different underlying CC causal diseases in terms of efficacy. Based on our observations, ESWL efficacy was better against small, ulcerated, and radiopaque CC, and it had an analgesic effect that might make subsequent surgical excision of CC fragments easier. Ergonomic adaptations are required to facilitate and expand ESWL use in dermatology.

Multiple Spreading Epidermolytic Acanthomas of the Genital and Perigenital Skin

Epidermolytic acanthoma is an uncommon benign tumour mainly characterized histologically by a prominent epidermolytic degeneration of the keratinocytes of the upper layers of the stratum spinosum and of the stratum granulosum. The absence of desmosome involvement allows to differentiate this condition from others such as acantholytic acanthoma. We report the first case, to our knowledge, of a 54-year-old male patient exhibiting disseminated scrotal, gluteal, inguinal and perineal epidermolytic acanthomas.

Effectiveness of Infliximab in Pityriasis Rubra Pilaris Is Associated with Pro-Inflammatory Cytokine Inhibition

Background: Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease. Recently, the use of anti-TNF-α in treating resistant forms of PRP has been reported. Objectives: To evaluate the clinical efficacy of infliximab in the treatment of PRP along with the evolution of secretion of some serum cytokines during treatment. Methods: Patients presenting widespread PRP were included consecutively and treated with infliximab. We compared cytokine profiles (notably CXCL-10 and TNF-α) by ELISA in sera from both patients with PRP and controls (healthy/psoriasis) at the time of diagnosis and after clinical remission (PRP). Results: 4 patients were treated with infliximab and achieved complete remission without any recurrence after treatment ending. The serum level of TNF-α and CXCL-10 was increased at the time of inclusion and normalized after treatment. Analysis of the typical component of the T helper cell 1 (Th1) and Th2 cytokine network did not show modification. Conclusion: Infliximab is an effective treatment of PRP. The analysis of the cytokine profile is in agreement with an absence of further recurrence of PRP by an early and unique inflammatory mechanism without significant underlying autoimmunity.

Assessment of bullous pemphigoid disease area index during treatment: a prospective study of 30 patients.

Background: Recently, a consensus Bullous Pemphigoid Disease Area Index (BPDAI) was proposed to measure therapeutic outcomes in bullous pemphigoid (BP). Objective: To compare BPDAI with other clinical parameters of disease activity at baseline and to describe the variations of BPDAI during the initial phase of treatment. Methods: Thirty BP patients were included and followed for 1 year. BPDAI was assessed at baseline and on days 30, 90 and 360 by the same investigator. Concomitantly, the number of daily new blisters, the skin surface area of erythematous/eczematous/urticarial plaques and blisters/erosions, total lesion area (TLA), pruritus score and mucosal involvement were recorded. Results: At baseline, BPDAI was 46.7 ± 25 (mean ± SD); it was well correlated with erythematous/eczematous/urticarial skin surface (r = 0.63), TLA (r = 0.83), number of daily new blisters (r = 0.7; p ≤ 0.0002) and anti-BP180 autoantibodies (r = 0.49; p = 0.006), but not with anti-BP230 autoantibodies. For the 8 patients with severe BP at baseline, the mean BPDAI was 76.5, versus 35.9 for moderate BP (p = 0.0007). A value of 56 was proposed as a cut-off value for severe BP. BPDAI decreased to 11.9 ± 8.7, 10.7 ± 12.7 and 2.5 ± 4.1 on days 30, 90 and 360, respectively. Conclusion: BPDAI rapidly decreased during the early treatment stage of BP with variations almost totally conditioned by the skin activity component.

Neurolymphomatosis associated with Sézary syndrome.

BACKGROUND Mycosis fungoides and Sézary syndrome are cutaneous T-cell lymphomas characterized by the epidermotropism of tumor cells. Neuropathic disease is rare during mycosis fungoides and Sézary syndrome and usually results from a central nervous system involvement in late stages. Neurolymphomatosis is defined as the infiltration of the peripheral nerves by tumor lymphocytes. It has been described in patients with aggressive systemic lymphomas but, to our knowledge, not in patients with mycosis fungoides or Sézary syndrome. We report the first case of neurolymphomatosis in a patient with Sézary syndrome and the partial efficacy of high-dose methotrexate sodium in treating this usually refractory complication. OBSERVATION A 73-year-old woman with newly diagnosed Sézary syndrome rapidly developed severe peripheral neuropathic disease with multiple paralyses. Biopsy specimens were taken from a clinically affected nerve and the adjacent muscle; they revealed a neural infiltration by Sézary cells with secondary muscular atrophy. Partial response and major neurologic recovery occurred and persisted under high doses of intravenous methotrexate until the patient died 14 months after the Sézary syndrome diagnosis from a pericarditis of uncertain origin. CONCLUSION This unusual and demonstrative case report highlights the possible neurotropism of malignant cells in Sézary syndrome and suggests the effectiveness of high doses of intravenous methotrexate in this rare and fatal disorder.

Melanoma, Past Severe Sunburns and Multiple Solar Lentigines of the Upper Back and Shoulders

Background: Multiple solar lentigines of the upper back and shoulders (MSLBS) have recently been demonstrated as being associated with intense sunburns in the past. Objective: To determine the prevalence of MSLBS among patients with cutaneous melanoma. Methods: Thisprevalence study was conducted prospectively from October 2003 to November 2004 in a single department of dermatology (Reims University Hospital, north of France). One hundred and twenty-five adult patients, followed up for a cutaneous melanoma, were included, and the prevalence of MSLBS was determined, with comparison of clinical characteristics of patients with and without these lesions. Results: The prevalence of MSLBS among patients with cutaneous melanoma was 37.6%. MSLBS were significantly and independently associated with cutaneous melanoma of the back in multivariate analysis (adjusted odds ratio, OR = 4.3, 95% confidence interval, CI = 1.5–12.3) and with recalled episodes of severe sunburn before the age of 28 (OR = 3.4, 95% CI = 1.3–9.4). Conclusion: Large irregularly shaped brown macules of the upper back and shoulders or MSLBS are frequent among adult patients with cutaneous melanoma. They are associated with melanoma located on the upper back. This topographical association further illustrates the relation between past intense sunburns and cutaneous melanoma. MSLBS should be evaluated as an easily recognizable clinical marker of the risk of cutaneous melanoma.

Efficacy and Safety of Methotrexate Combined with Low- to Moderate-Dose Corticosteroids for Severe Alopecia Areata

Background: In severe alopecia areata (AA), spontaneous recovery is unlikely, and treatment is not standardized. Objective: To evaluate the efficacy and safety of methotrexate (MTX) used alone or combined with low- to moderate-dose oral corticosteroids (OC) for treating severe AA (totalis, universalis and severe multifocal). Methods: Retrospective monocentric study of all consecutive patients receiving this treatment between 2006 and 2012. Efficacy was defined as achieving a total regrowth of terminal hair. Results: 26 patients were included (17 with AA universalis or totalis and 9 with severe multifocal AA). Total regrowth was noted in 15/26 patients. After 3 months of treatment, hair regrowth >80% was associated with further complete regrowth, and hair regrowth <30% was associated with later treatment failure (p = 0.0014). When treatment was tapered, 11/15 patients with initial complete efficacy experienced AA relapse. Conclusion: MTX combined with low- to moderate-dose OC may be an efficient and well-tolerated treatment for severe AA. However, long-term maintenance treatment is usually required.

Usefulness of skin testing in cutaneous drug eruptions in routine practice.

Background: Cutaneous drug eruptions are common side‐effects. The imputation score combining intrinsic (chronology, clinical and paraclinical signs) and extrinsic criteria used in Pharmacovigilance Centres is insufficient alone to identify with certainty a responsible drug.