Treatment of dissecting cellulitis of the scalp with tumour necrosis factor inhibitors: a retrospective multicentre study.

Although retinoids are considered as the most effective treatment, management of dissecting cellulitis of the scalp (DCS) is often challenging. A multicentre retrospective study was conducted to evaluate the efficacy of anti-tumour necrosis factor (TNF) agents in treating DCS after failure of other conventional treatments. Twenty-six patients were included. After a mean treatment duration of 19 months (SD 21), the median Physician's Global Assessment score decreased from 3 to 1. The median number of inflammatory nodules and abscesses decreased from 7 to 0.5 and from 1 to 0, respectively. The median Dermatology Life Quality Index and numerical rating scale score for pain severity decreased from 10 to 8 and 6 to 1, respectively. The median treatment satisfaction was 7 out of 10 on the Patient Satisfaction Index. This study confirms the efficacy of anti-TNF agents in treating patients with DCS that is resistant to conventional therapies.

Biological Therapies or Apremilast in the Treatment of Psoriasis in Patients with a History of Hematologic Malignancy: Results from a Retrospective Study in 21 Patients.

BACKGROUND: Few studies addressing the safety and efficacy of biological therapy (BT) or apremilast (APR) in patients with psoriasis with a history of hematologic malignancy (HM) exist. AIM: To describe the tolerance and efficacy of BT and APR in moderate-to-severe psoriasis in patients with a history of in-remission or evolving HM. METHODOLOGY: A retrospective, multicenter chart review of the tolerance and efficacy of BT or APR in patients with moderate-to-severe psoriasis and a clinical history of in-remission or evolving HM. RESULTS: Twenty-one patients with severe psoriasis and a history of HM were included in France by the GEM Resopso study group. Of the 16 patients treated with one or more BT lines, none showed recurrence of their HM which was considered as stable or in remission, and only 2 patients showed an evolution of their HM which had been considered as stable at the beginning of treatment. In the 10 patients treated with APR, the HM of one patient who also received BT worsened. The 3 evolutions did not impact the treatment with BT or APR. Tolerance was very satisfactory, with a low occurrence of infections. Regarding efficacy, only one patient treated with APR did not achieve any notable clinical improvement. CONCLUSION: Despite supportive data regarding tolerance, the heterogeneity of the analyzed population and limited available data, BT and APR should be used with caution in this patient population and investigations on larger cohorts should be conducted to further assess their tolerance in this patient population.

Psychometric validation of a patient-reported outcome questionnaire (Qualipsosex) assessing the impact of psoriasis and psoriatic arthritis on patient perception of sexuality.

ABSTRACT: Psoriasis (Pso) and psoriatic arthritis (PsA) frequently have a negative impact on patients' sexual health. We have developed a specific questionnaire assessing the impact of Pso and PsA on patient perception of sexuality: the QualipsoSex Questionnaire (QSQ). The aim of the present study was to further validate this questionnaire by checking its psychometric properties including validity, reliability, and responsiveness.A cross sectional observational study with a longitudinal component for responsiveness and test-retest reliability was performed in 12 centers in France including 7 dermatologists and 5 rheumatologists. Psychometric properties were examined according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) check-list.At baseline, 114 patients had Pso and 35 patients had PsA including 17 peripheral arthritis, 4 axial disease, 13 patients with both axial disease and peripheral arthritis and one patient with an undifferentiated phenotype. The mean Pso Area and Severity Index score was 12.5. Genital organs were involved in 44.7% of Pso cases. Internal consistency, construct validity, and reliability were good with Cronbach's α coefficient, measure of sampling adequacy and intraclass correlation coefficient respectively at 0.87, 0.84, and 0.93. The QSQ also demonstrated acceptable sensitivity to change.The QSQ has demonstrated good psychometric properties fulfilling the validation process relative to the recommendations of the COSMIN check list. The QSQ is simple to score and may hopefully be valuable in clinical practice and in clinical trials.

Matrix remodelling and MMP expression/activation are associated with hidradenitis suppurativa skin inflammation.

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle, associated with considerable tissue remodelling. Although abnormal cytokine expression was detected both in perilesional and in uninvolved skin, up to now there is no model allowing a better understanding of the implicit inflammatory mechanisms in HS. The aim of this study was to investigate the inflammatory response in HS skin by mean of an ex vivo model culture. To that purpose, nine skin biopsy specimens from patients suffering from HS and controls were cultured up to 4 days. Microscopy imaging investigations showed variations of collagen I and III organization, and an increase in elastin fibres fragmentation in HS skin after 4 days of culture. The HS matrix structure remodelling was associated with high level of MMP-2 and MMP-9 in HS lesional skin. After 4 days of culture, the MMP expression in HS perilesional skin reached the level observed in HS lesional skin. Concomitantly, an increase in IL-1ß concentration was observed in all skin samples after 4 days of culture, although IL-1ß concentrations remained significantly higher in HS lesional skin as compared with control skin. Meanwhile, neither IL-17 concentrations nor the inflammasome components NLRP3 and caspase-1 varied. Thus, our HS skin model culture showed that MMP-induced matrix alteration could participate in HS inflammation by releasing biological active peptides and inflammatory factors from the extracellular matrix (ECM), and open new opportunities to investigate the regulation of the inflammatory mechanism associated with HS.

Ustekinumab for skin reactions associated with anti-tumor necrosis factor-α agents in patients with inflammatory bowel diseases: A single-center retrospective study.

Anti-tumor necrosis factor (TNF)-α agents may induce skin reactions, in particular in patients with inflammatory bowel diseases (IBD). The objective of this study was to determine the efficacy of ustekinumab in these patients. IBD patients facing therapeutic issues because of cutaneous reactions or tolerance issues, consequently treated with ustekinumab in our department, were included. Retrospective review of case records and clinical photographs was carried out. Twenty-six patients were included. Twenty-three patients were treated for Crohn's disease and three for ulcerative colitis. Fourteen patients presented psoriasiform lesions, nine eczematiform lesions, four anaphylactoid reactions, two alopecia areata-like lesions, one injection-site reaction, one cutaneous polyarteritis nodosa and five other skin reactions. Most of them resolved under ustekinumab. In detail, eczematiform lesions completely resolved in all cases, psoriasiform lesions completely resolved in 12 cases (85.7%) and had partial response in two cases (14.3%). Two cases of alopecia areata showed complete response (complete hair regrowth). Fourteen patients showed complete digestive response, 10 patients partial digestive response (seven of which needed IBD treatment optimization) and only two failure. In conclusion, ustekinumab is a drug of choice in patients with IBD who cannot tolerate TNF blockers.

Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa. METHODS: PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS: We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS: Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

[Efficacy and safety of ustekinumab in psoriatic arthritis after anti-TNFα failure in routine practice]. / Ustekinumab dans le rhumatisme psoriasique après échec des anti-TNFα en pratique courante.

PURPOSE: Evaluation of effectiveness and safety of ustekinumab in psoriatic arthritis after anti-TNFα failure. METHODS: We conducted a retrospective and monocentric study. The evaluation of articular and cutaneous effectiveness by the patient was made with numeric scale and satisfaction scale and by the physician during a rhumatological-dermatological consultation. The safety was analyzed by collecting the adverse effects. RESULTS: Nine patients with anti-TNF failure were included. Five of them stopped the treatment because of severe adverse effects. The mean duration treatment of ustekinumab was 24 months. Articular and cutaneous effectiveness were respectively 4.4/10 and 6.7/10. Two thirds of the patients were "satisfied" and one third could stop any analgesic treatment. The mean PASI score decreased from 8.4 to 1.7 after 3 months treatment. Only minor adverse effects were collected and there were no recidivism of the adverse effects observed with anti-TNFα. CONCLUSION: Ustekinumab is an effective and safe alternative for patients with anti-TNFα failure in psoriatic arthritis.

Development of monoclonal gammopathy under biotherapy in psoriasis: a French multicenter retrospective study.

BACKGROUND: Biotherapies or targeted therapies are fairly new treatments indicated for moderate to severe psoriasis. The side effects appear to be mainly infectious or cancerous. The role of biotherapies in the development of a pre-cancerous condition, monoclonal gammopathy of undetermined significance (MGUS), has recently been debated in the literature. OBJECTIVES: To evaluate the incidence of MGUS in psoriasis patients treated with biotherapy. MATERIALS AND METHODS: This study was a French multicenter retrospective study carried out through the French multicenter study group RESOPSO. Data on the results of serum protein electrophoreses performed before and within at least six months after the start of the biotherapy were collected. Demographic data, medical history, and psoriasis treatment history were specified. RESULTS: Four hundred and forty three patients were eligible for inclusion. Of these, three presented with monoclonal gammopathy for which the assessment was in favor of MGUS. The average treatment period was 19.7 months. Six patients presented with MGUS prior to the treatment. These patients' immunoglobulin levels remained stable, with an average remission of 24 months. Only psoriatic rheumatism appeared to be statistically linked to MGUS. CONCLUSION: The incidence and frequency of MGUS in psoriasis patients treated with biotherapy do not appear to increase relative to the general population.

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.

[Cutaneous adverse reactions of EGFR (epidermal growth factor receptor)-inhibitors: therapeutic algorithm of the French PROCUR group]. / Toxicité cutanée des anti-EGFR (epidermal growth factor receptor) : algorithme thérapeutique du groupe français PROCUR.

The epidermal growth factor receptors (EGFR)-inhibitors are frequently responsible for cutaneous adverse drug reactions that may alter the patients' quality of life and hamper the continuation of treatment. We present here the experience of a group of French multidisciplinary experts - the PROCUR group (PRise en charge de la tOxicité CUtanée des anti-EGFR) - created in order to establish a therapeutic algorithm. It was built in three steps under the responsibility of a steering committee: (1) a systematic literature review was performed by a group of three dermatologists and one oncologist; (2) regional meetings evaluated practical aspect of the treatments in France; (3) a final meeting confrontating the practices in France and the evidence-based medicine including the steering committee, the bibliographic group, and oncologists, radiotherapists, dermatologists and hepato-gastroenterologists involved in regional scientific committees, resulted in a therapeutic algorithm, resulting in the collegial writing of this algorithm. This multidisciplinary study should facilitate the standardised, optimised management of skin toxicity associated with EGFR-inhibitors.

Efficacy and tolerance of prolonged infliximab treatment of moderate-to-severe forms of hidradenitis suppurativa.

UNLABELLED: Hidradenitis suppurativa (HS) is a chronic suppurative disease impairing patients' quality of life (QOL). The standard treatment remains extensive surgery; medical treatment is often disappointing. OBJECTIVES: Prolonged infliximab efficacy and tolerance in moderate-to-severe forms of HS were evaluated. PATIENTS AND METHODS: This prospective, monocentric, open, interventional study concerned patients with progressive, moderate-to-severe HS ineligible for surgery, or who relapsed after surgery. Infliximab (5 mg/kg) was infused at weeks 0, 2 and 6, and then every 4 weeks. When the response was satisfactory, infusion spacing was attempted. RESULTS: Ten patients were included, 8 treated for 1 year, with a mean of 5 affected sites and 18 years of evolution. The mean initial DLQI was 20/30 (range 9-30). At 1 year, the number of involved sites (P<0.001) and flares (P<0.05) had decreased significantly under infliximab, as did HS severity. QOL improved clearly and rapidly for all patients, with mean DLQI at 6/30 (P<0.001). Tolerance was satisfactory with only 4 minor infections, 1 keratoacanthoma and one rapidly resolving hepatitis. CONCLUSION: This evaluation of prolonged infliximab use in HS after surgical failure showed good efficacy and satisfactory tolerance without therapeutic escape during the first year of treatment.

Folliculitis induced by EGFR inhibitors, preventive and curative efficacy of tetracyclines in the management and incidence rates according to the type of EGFR inhibitor administered: a systematic literature review.

INTRODUCTION: Folliculitis is the most common side effect of epidermal growth factor receptor (EGFR) inhibitors (EGFRIs). It is often apparent, altering patients' quality of life and possibly impacting compliance. Variations in terms of the treatment-related incidence and intensity have not been fully elucidated. Tetracyclines have been recommended for the prophylaxis and treatment of folliculitis but their efficacy is yet to be established. MATERIALS AND METHODS: We carried out two systematic literature reviews. The first assessed the preventive and curative efficacy of tetracyclines. The second assessed the incidence of grade 3-4 folliculitis in the main clinical studies published. RESULTS: In four randomized studies, preventive tetracycline treatment was associated with a significantly lower incidence of grade 2-3 folliculitis and a better quality of life in three of the four studies. In curative terms, tetracycline efficacy was not evaluated in any randomized study, but an improvement in grade ≥2 folliculitis was reported in case series. The frequency and severity of folliculitis seem to be greater with the antibodies than with the tyrosine kinase inhibitors. Analysis restricted to lung cancer studies showed a statistically greater incidence in terms of grade 3-4 folliculitis with cetuximab (9%) and erlotinib (8%) than with gefitinib (2%) (p < .0001). CONCLUSION: Unless contraindicated, a tetracycline should be routinely prescribed prophylactically for patients treated with an EGFRI (level of evidence, B2). In curative therapy, the level of evidence for tetracycline efficacy is low (level of evidence, D). The incidence of grade 3-4 folliculitis induced by EGFRIs appears to be lower with gefitinib.

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.

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.

Long-term survivors in stage IV melanoma: a regional population-based study in France.

We aimed to better characterize exceptional cases of long survivors (LSs) among patients with stage IV melanoma. We performed a comprehensive regional investigation in the Champagne-Ardenne region, France. During the period 1994-2003, 316 patients died of melanoma whereas 10 patients diagnosed with distant metastases had a subsequent survival time > 4 years. These 10 LSs were characterized by a long delay (median: 58 months) prior to distant metastases and by frequent subsequent complete remissions (CRs). Eighteen episodes of CRs, lasting 3-139 months (mean: 26.4), were documented in 9 patients, for single or multiple tumors, for metastases of any site and with any treatment, even including spontaneous CRs. Four of 8 evaluable patients had clinical and/or biological features of auto-immunity. At 31 March 2007, 3 patients had died of melanoma and 1 of a chemo-induced leukaemia. The median survival time was 65 months (range: 52-139). These data suggest that long survival in stage IV melanoma might depend less on the site of metastases and specific therapies than on the patients themselves and their spontaneous antitumor control.

Thiopurine S-methyltransferase genotypic analysis in autoimmune bullous diseases.

Thiopurine S-methyltransferase (TPMT) activity is inversely related to the risk of developing severe hematopoietic toxicity in patients treated with azathioprine. The aim of this study was to evaluate the usefulness of TPMT genotyping in severe cases of autoimmune bullous diseases treated with azathioprine. A retrospective study of TPMT genotyping was performed in patients with autoimmune bullous diseases hospitalized in a single centre between 1999 and 2006 and susceptible of being treated by azathioprine. Among 75 patients tested, 70 (93%) had a high TPMT activity and 5 (7%) an intermediate activity. TPMT genotyping was performed in 33/34 patients currently treated with azathioprine. Haematopoietic side-effects (usually moderate) were observed in 12/34 patients treated with a mean dosage of 2.7 mg/kg/day and occurred, despite a high predicted TPMT activity. No myelotoxicity was observed in the two patients with intermediate predicted TPMT activity (mean dosage: 1.7 mg/kg/day), who obtained a clinically complete remission. Although strongly recommended before azathioprine treatment, predicting TPMT activity appears only marginally helpful in patients with autoimmune bullous diseases, mainly for adjusting the azathioprine dosage. In addition, a normal TPMT genotyping is not a guarantee against the occurrence of haematological side-effects.

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.