P. Wolkenstein

Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis

BACKGROUND Toxic epidermal necrolysis (TEN) is associated with a 30% death rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN. METHODS The patients received a 5-day course of thalidomide 400 mg daily or placebo. The main endpoint was the progression of skin detachment after day 7. Secondary endpoints were the severity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were measured. FINDINGS The study was stopped because there was excess mortality in the thalidomide group--ten of 12 patients died compared with three of ten in the placebo group (Fishers exact test with Katzs approximation, relative risk=2.78, p=0.03). After adjustment for SAPS, mortality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was higher in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p=0.07). INTERPRETATION Even though few patients were included, our data suggest that thalidomide is detrimental in TEN, possibly because of a paradoxical enhancement of TNF-alpha production.

Prevalence and factors associated with hidradenitis suppurativa: Results from two case-control studies

BACKGROUND Conflicting opinions have been reported regarding the epidemiology of hidradenitis suppurativa. OBJECTIVE We sought to evaluate the prevalence of hidradenitis suppurativa and to identify associated factors. METHODOLOGY Prevalence was evaluated using a representative sample of the French population (n=10,000). Associated risk factors were assessed using two case-control studies, one population-based with 67 self-reported patients and 200 control subjects, and the other clinic-based with 302 medically assessed patients and 906 control subjects. RESULTS The prevalence was 1% of the French population. Multivariate analyses showed a strong association with current smoking in self-reported (odds ratio=4.16, 95% confidence interval [2.99-8.69]) and in medically assessed (odds ratio=12.55 [8.58-18.38]) populations. Association with body mass index was significant in medically assessed patients (odds ratio=1.12 [1.08-1.15]) for each increase of 1 U of BMI. LIMITATIONS A causal relationship could not be established with such a cross-sectional study. CONCLUSION Hidradenitis suppurativa is a common disease, frequently associated with smoking and being overweight.

Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis

Summary Toxic epidermal necrolysis (TEN) and Stevens‐Johnson syndrome (SJS) are life‐threatening diseases characterized by extensive epidermal destruction. The aim of our study was to investigate apoptosis in keratinocytes of patients with TEN and TEN/SJS overlap syndrome. Keratinocytes from TEN patients were found to undergo extensive apoptosis. These results suggest that cell destruction in TEN occurs as a result of apoptosis. Our findings suggest that apoptosis inhibitory agents may play an important part in the therapeutic strategy of TEN.

Repair of the lower and middle parts of the face by composite tissue allotransplantation in a patient with massive plexiform neurofibroma: a 1-year follow-up study

BACKGROUND The risk to benefit ratio of face transplantation with a composite tissue allograft remains debatable, although this procedure is technically feasible. We report here a 1-year follow-up of a patient who underwent face transplantation with a composite tissue allograft. METHODS On Jan 21, 2007, a 29-year-old man with neurofibromatosis type 1 underwent resection of a massive plexiform neurofibroma diffusely infiltrating the middle and lower part of his face. The main goal was to restore both the cutaneous appearance and function of the face, including, in particular, control of orbicularis oculi and oris muscle contraction. The issues of immunosuppressive therapy, psychological outcome, and social reintergration were addressed, together with the monitoring of graft rejection by biopsies of the skin and mucosa. FINDINGS The initial postoperative course was uncomplicated. Two episodes of clinical rejection occurred on days 28 and 64. The second episode was associated with cytomegalovirus infection. Both episodes resolved favourably, with no further clinical signs of rejection, making the reduction of immunosuppressive treatment possible. A year after surgery, the functional outcome was very good, with successful sensory and motor reinnervation in the transplanted territory. Psychological recovery was excellent, with complete social reintegration. INTERPRETATION This case demonstrates the feasibility of surgically removing a large part of the face and replacing it with a composite tissue allograft. This facial repair procedure, which seems to have a satisfactory risk to benefit ratio, could be offered in rare and selected cases.

Elevated Risk for MPNST in NF1 Microdeletion Patients

An NF1 microdeletion is the single most commonly reported mutation in individuals with neurofibromatosis type 1 (NF1). Individuals with an NF1 microdeletion have, as a group, more neurofibromas at a younger age than the group of all individuals with NF1. We report that NF1 microdeletion individuals additionally have a substantially higher lifetime risk for the development of malignant peripheral nerve sheath tumors than individuals with NF1 who do not have an NF1 microdeletion. This should be taken into account in the medical follow-up of individuals with an NF1 microdeletion.

Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study

AbstractObjective: To evaluate the incidence, clinical features, and prognosis of pulmonary complications associated with toxic epidermal necrolysis Design: Prospective study. Setting: Dermatology intensive care unit in Mondor Hospital, France. Patients: 41 consecutive patients. Interventions: On admission, then daily, respiratory evaluation was based on clinical examination, chest X-ray, and arterial blood gas analysis. When clinical symptoms, X-ray abnormalities, or hypoxemia [partial pressure of oxygen (PO2)<80 mm Hg] were present, fiberoptic bronchoscopy was performed. Results: 10 patients presented early manifestations: dyspnea (n=10), bronchial hypersecretion (n=7), marked hypoxemia (n=10) (PO2=59 ± 8 mmHg). Chest X-ray was normal (n = 8) or showed interstitial infiltrates (n=2). In these 10 patients, fiberoptic bronchoscopy demonstrated sloughing of bronchial epithelium in proximal airways. Delayed pulmonary complications occurred in 6 of these 10 patients from day 7 to day 15: pulmonary edema (n=2), atelectasis (n=1), bacterial pneumonitis (n=4). Mechanical ventilation was required in 9 patients. A fatal outcome occurred in 7 patients. Seven patients did not develop early pulmonary manifestations (PO2 on admission 87 ± 6 mm Hg) but only delayed pulmonary symptoms related to atelectasis (n=1), pulmonary edema (n=4), and bacterial pneumonitis (n=3); bronchial epithelial detachment was not observed. None of them required mechanical ventilation and all recovered with appropriate therapy. Conclusions: “Specific” involvement of bronchial epithelium was noted in 27 % of cases and must be suspected when dyspnea, bronchial hypersecretion, normal chest X-ray, and marked hypoxemia are present during the early stages of toxic epidermal necrosis. Bronchial injury seems to indicate a poor prognosis, as mechanical ventilation was required for most of these patients and was associated with a high mortality.

Open trial of ciclosporin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis.

Background  Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute mucocutaneous reactions associated with poor prognosis. The treatment is mainly symptomatic, based on supportive care. Until now, several curative treatments have been proposed without evidence of effectiveness.

Combination Therapy with Clindamycin and Rifampicin for Hidradenitis Suppurativa: A Series of 116 Consecutive Patients

Background: Antibiotics are frequently used to treat hidradenitis suppurativa (HS); however, few data on their efficacy are available. Objective: To evaluate the efficacy of a combination of systemic clindamycin (300 mg twice daily) and rifampicin (600 mg daily) in the treatment of patients with severe HS. Methods: Patients (n = 116) who received this combination were studied retrospectively. The main outcome measure was the severity of the disease, assessed by the Sartorius score, before and after 10 weeks of treatment. Results: The Sartorius score dramatically improved at the end of treatment (median = 29, interquartile range = 14.5, vs. median = 14.5, interquartile range = 11; p < 0.001), as did other parameters of severity as well as the quality of life score. Eight patients (6.9%) stopped the treatment because of side effects. Conclusion: The combination of clindamycin and rifampicin is effective in the treatment of severe HS.

NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype

In 5‐10% of patients, neurofibromatosis type 1 (NF1) results from microdeletions that encompass the entire NF1 gene and a variable number of flanking genes. Two recurrent microdeletion types are found in most cases, with microdeletion breakpoints located in paralogous regions flanking NF1 (proximal NF1‐REP‐a and distal NF1‐REP–c for the 1.4 Mb type‐1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Mb type‐2 microdeletion). A more severe phenotype is usually associated with NF1 microdeletion patients than in those with intragenic mutations. We characterized NF1 microdeletions in 70 unrelated NF1 microdeleted patients using a high‐resolution NF1 custom array comparative genomic hybridization (CGH). Genotype‐phenotype correlations were studied in 58 of these microdeletion patients and compared to 389 patients with intragenic truncating NF1 mutations and phenotyped in the same standardized way. Our results confirmed in an unbiased manner the existence of a contiguous gene syndrome with a significantly higher incidence of learning disabilities and facial dysmorphism in microdeleted patients compared to patients with intragenic NF1 mutations. Microdeleted NF1 patients also showed a trend toward significance for childhood overgrowth. High‐resolution array‐CGH identified a new recurrent ∼1.0 Mb microdeletion type, designated as type‐3, with breakpoints in the paralogous regions middle NF1‐REP‐b and distal NF1‐REP–c.

Clinical characteristics of a series of 302 French patients with hidradenitis suppurativa, with an analysis of factors associated with disease severity

BACKGROUND Factors associated with the severity of hidradenitis suppurativa (HS) are not known. OBJECTIVE We sought to identify factors associated with the severity of HS. METHODOLOGY The severity of disease in a series of 302 consecutive patients with HS was assessed using the Sartorius score. RESULTS Atypical locations were more common in men than in women (47.1% vs 14.8%; P < .001). Men also had more severe disease (median Sartorius score: 20.5 vs 16.5; P = .02). Increased body mass index (P < .001), atypical locations (P = .002), a personal history of severe acne (P = .04), and absence of a family history of HS (P = .06) were associated with an increased Sartorius score. The Sartorius score was highly correlated with the intensity and duration of pain and suppuration (all P values < .001). LIMITATIONS The referral center base of the study may have biased recruitment. CONCLUSION Our data showed a significant association between the severity of HS and several clinical and behavioral factors. Prospective studies are needed to confirm the prognostic role of these factors.