Treatment of Acne with Isotretinoin Should Be Avoided in Patients with Hidradenitis Suppurativa "Conglobata Phenotype".

BACKGROUND: Acne conglobata (AC) and nodulocystic acne have long been confused clinically, despite the presentation and the response to treatment being different. AC and hidradenitis suppurativa (HS) resemble each other; a subtype of HS called "conglobata phenotype" has recently been reported in a large Dutch cohort. Acne vulgaris and HS are often associated. Isotretinoin is typically ineffective in treating HS and may even aggravate it, but it is often indispensable in treating acne vulgaris. OBJECTIVE: The aim of the study was to assess whether isotretinoin may be used safely in adults with both HS and acne vulgaris and when it might be contraindicated. MATERIALS AND METHODS: Belgian HS patients from the European Registry for Hidradenitis Suppurativa Registry (ERHS) reporting a history of severe acne of the face and/or the back, and who have ever used isotretinoin for their acne, were all selected. Patients whose acne worsened on isotretinoin were compared to patients whose acne did not worsen (improvement or no change). RESULTS: Among the 82 selected patients, 10 (12.2%) report that their acne was aggravated while taking isotretinoin, while 72 (87.8%) report that their acne was not aggravated on isotretinoin. Of the 10 HS patients whose acne worsened with isotretinoin, 9 (90%) were men (p = 0.04) and 8 (80%) were HS "conglobata phenotype" (p < 0.001). In contrast, 47 (65.3%) of the 72 patients whose acne did not worsen on isotretinoin belonged to the HS "regular phenotype" (p = 0.01). On multivariate analysis, the item most strongly associated with poor response to isotretinoin was the HS "conglobata phenotype," followed by body mass index (BMI) (worse response to isotretinoin if BMI >25 kg/m2). Additionally, of 26 patients who received isotretinoin while their HS had already started, only 6 (23.1%) reported isotretinoin effectiveness on their HS. CONCLUSION: Subject to confirmation by larger studies, our study suggests that isotretinoin should be avoided in the treatment of acne in HS patients with the HS "conglobata phenotype," as it may worsen the acne, likewise being male or having a BMI above 25 seems to increase this risk of a bad therapeutic outcome. Patients with an HS "regular phenotype" appear to be at a reduced risk of isotretinoin treatment worsening their acne.

Proposed Definitions of Typical Lesions in Hidradenitis Suppurativa.

BACKGROUND: Although not rare, hidradenitis suppurativa (HS) is often under-recognized by physicians. The diagnosis of HS is clinical via the recognition of lesions typical of the disease, but universally accepted definitions of these latter are currently lacking, which means that certain severity scores employed for HS classification/management are used differently by different physicians. Our aim was to develop a set of descriptive definitions and associated images of HS lesions, in order to enable doctors to better recognize and evaluate the disease. METHODS: MEDLINE-available literature and dermatological textbooks on HS morphology were retrieved (January 1996 to February 2016). A preliminary set of definitions of HS typical lesions was created, including 10 terms. Each term was associated with a pathophysiological classification and an image. This preliminary set was shown during the 5th Conference of the European HS Foundation (EHSF). The physicians attending the event were invited to vote on each term and make comments via a voting sheet. RESULTS: A total of 81 physicians answered the questionnaire. Their agreement/disagreement rates and comments were used to obtain a revised set of definitions and images. Pathophysiological classifications were dropped. CONCLUSION: A user-friendly set of definitions/images of HS typical lesions was proposed and will need to be validated by further studies. This set could ultimately serve as a tool to better recognize, score, and assess treatment efficacy.

New Evidence Supporting Cyclosporine Efficacy in Epidermal Necrolysis.

Sixty years after its original description by Sir Alan Lyell, epidermal necrolysis (from Stevens-Johnson syndrome to toxic epidermal necrolysis) seems finally amenable to a specific treatment in addition to essential symptomatic measures in specialized settings. A recently published systematic review and an article by Gonzales-Herrada et al. strongly suggest that cyclosporine is effective in reducing the risk of death.

Diagnosing Hidradenitis Suppurativa.

Three diagnostic criteria must be met for hidradenitis suppurativa: typical lesions, occurrence in one or more of the predilection areas, and that it is chronic and/or recurrent. Several outcome measures are used, including patient-reported pain and itch scales, Dermatology Life Quality Index, and Skindex. Hidradenitis suppurativa is associated with significant comorbidities that must be addressed in the evaluation of the patients.

A randomized, investigator-masked, double-blind, placebo-controlled trial on thalidomide in severe cutaneous sarcoidosis.

BACKGROUND: Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. The objective of this study was to evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis. METHODS: This study consisted of a randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicenter trial lasting 3 months and an open-label study from month 3 to month 6. Adults with a clinical and histologic diagnosis of cutaneous sarcoidosis were included in nine hospital centers in France. Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for 3 months. In the course of an open-label follow-up from month 3 to month 6, all patients received thalidomide, 100 mg to 200 mg daily. The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement in three target lesions scored for area and infiltration, were compared across randomization groups. RESULTS: The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients in the thalidomide group (20%) vs four out of 19 patients in the placebo group (21%) had a partial cutaneous response at month 3 (difference in proportion of -1% [95% CI, -26% to +24%] for thalidomide vs placebo, P = 1.0). Eight patients with side effects were recorded in the thalidomide group vs three in the placebo group. We observed a large number of adverse event-related discontinuations in patients taking thalidomide in the first 3 months (four patients with thalidomide, zero with placebo) and in the 3 following months (five patients). CONCLUSIONS: At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT0030552; URL: www.clinicaltrials.gov.

Prognostic value of histologic features of toxic epidermal necrolysis.

BACKGROUND: The prognosis of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and SJS/TEN overlap syndrome has been assessed using a disease-specific severity score (SCORTEN) based on clinical and laboratory data. Histologic data may improve outcome prediction. OBJECTIVE: We sought to evaluate whether dermal mononuclear infiltration and epidermal necrosis predict survival of patients with TEN, SJS, or SJS/TEN. METHODS: We conducted a retrospective review of clinical records and skin biopsy specimens read without knowledge of clinical data. RESULTS: We identified 108 patients (SJS, n = 42; SJS/TEN, n = 36; TEN, n = 30). Overall mortality was 21.3%. Dermal infiltration and epidermal necrosis were not associated with time from disease onset to biopsy. Extensive dermal infiltrates were seen in 19 (18.5%) patients and full-thickness epidermal necrosis in 56 (52%) patients. Dermal infiltrate severity was not associated with day-1 (D1) SCORTEN or hospital death. Epidermal necrosis severity showed trends toward associations with D1 SCORTEN (P = .11) and hospital death (P = .06). In univariate analyses, full-thickness epidermal necrosis was significantly associated with hospital death (32.1% vs 11.4%, P = .017) and worse D1 SCORTEN values (1.98 ± 1.29 vs 1.55 ± 1.21; P = .04). In the bivariate analysis, however, D1 SCORTEN remained significantly associated with hospital death (odds ratio = 3.07, 95% confidence interval 1.83-5.16) but the association with full-thickness epidermal necrosis was no longer significant (odds ratio = 2.02, 95% confidence interval 0.65-7.12). LIMITATIONS: Retrospective study design and indirect assessment of progression are limitations. CONCLUSION: Full-thickness epidermal necrosis was associated with mortality but did not independently predict hospital death after adjustment based on the SCORTEN value. Dermal infiltrate severity was not associated with hospital death.

Identification of three hidradenitis suppurativa phenotypes: latent class analysis of a cross-sectional study.

To identify the underlying subtypes of hidradenitis suppurativa (HS), we performed latent class analysis on prospective clinical data of 618 consecutive patients seen between 2002 and 2010. The median patient age was 31 years (Q1=26; Q3=38), median age at HS onset was 20 years (16-25), and median Sartorius score was 18 (11-19); 34.4% of patients were of Hurley stage II or III. A three-class model showed the best fit. Latent class 1 (LC1) patients (48%) had a high probability of breast and armpit lesions (0.74) and hypertrophic scars (0.41). LC2 patients (26%) had a high probability not only of breast and armpit lesions (0.96) but also of lesions in the ears, chest, back, or legs (0.55); follicular lesions (pilonidal sinus: 0.48; comedones: 0.74); severe acne (0.47); and a family history of HS (0.44). Compared with LC1 patients, LC2 patients were more often male (odds ratio, 4.6; 95% confidence interval, 3-7; P<0.001) and current smokers (2.2; 1.3-3.9; P=0.005), and had greater disease severity (odds ratio, 1.6; 1.3-1.9; P<0.001). LC3 was characterized by gluteal involvement (0.54), papules, and folliculitis (0.71). LC3 patients were less often obese (0.6; 0.3-0.95; P=0.03) and had less severe disease (0.9; 0.7-1.1; P<0.001). These three phenotypes ("axillary-mammary", "follicular", and "gluteal") may help stratify patients for clinical trials.

Acne as seen by adolescents: results of questionnaire study in 852 French individuals.

Acne can have an important psychological impact. We surveyed 852 adolescents aged 12-25 years about their knowledge of acne and its treatment in a non-medical context. The study involved a questionnaire administered to callers to a youth telephone helpline in France. Callers were categorized into those who currently had acne, those who had had acne previously, and those who had never had acne. Most respondents (66.2%) had experienced acne symptoms, which were mild in 50.2% of cases and severe in 16% of cases. Often, acne had been long-lasting (>12 months in 49.6% of cases). Many thought that gender, excess weight, eating dairy products, and physical activity did not influence acne, and that frequent washing could improve acne. Eating chocolate and snacks, smoking cigarettes, sweating, not washing, touching/squeezing spots, eating fatty foods, using make-up, pollution, and menstruation were thought to worsen acne. The majority (80.8%) did not believe acne to be a disease, but rather a normal phase of adolescence, yet 69.3% agreed it should be treated. There was a preference for topical vs. systemic treatment. Many (38.6%) of the respondents with acne had not consulted a physician. Almost two-thirds of respondents wanted more information about acne. Providing more information about acne might increase the likelihood of them consulting a physician and getting better treatment for the condition.

Hidradenitis suppurativa.

Hidradenitis suppurativa, or Verneuil's disease, is somewhat common, especially in women, but it often unrecognized. Clinical manifestations include painful nodules, abscesses, sinus tracts, and ropelike hypertrophic scars in the apocrine gland-bearing areas. It is a chronic disease. Smoking and overweight are risk factors, but the cause is unknown: it is a disease of the follicular apparatus, neither infectious nor hormonal. Severe dramatic forms are rare. Quality of life is severely affected even in the mild forms. Treatment is both medical and surgical: wide-spectrum antibiotics and excisions tailored to the extent of involvement. Anti-TNFα drugs are effective, but their risk-benefit ratio is still in question. Laser treatment is under study.

Back and face involvement in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) may be associated with face and back lesions which are considered as acne. OBJECTIVE: To describe the skin lesions of a group of patients with HS. METHODS: Twelve patients were selected from a series of 648 patients on the basis of their specific skin lesions. RESULTS: The patients (mostly male) had typical hidradenitis. On their face or back they had one or several of the following skin lesions which are not seen in acne: hypertrophic rope-like bridged scars, raised plaques with multiple carbuncle-like openings or with ulcerations, 'worm-eaten scars' and coalescent nodules with round ulcerations. All patients had deep round scars. Several had a pilonidal cyst or large epidermal cysts. Isotretinoin had been used by 7 patients with no effect. CONCLUSION: Some HS patients have specific lesions of the face and back which are not acne and have to be treated differently.

Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis.

Severe recurrent aphthous stomatitis (SRAS) is a rare, disabling disorder of unknown etiology. Thalidomide is an effective second-line therapy for SRAS, but is suppressive rather than curative, and adverse events limit its use. Few reports describe the efficacy, tolerance, and safety of thalidomide, and how it is actually used as long-term (maintenance) therapy for SRAS. Therefore, we conducted this study to describe thalidomide use in the real-life management of a cohort of patients with SRAS. This multicenter retrospective cohort study covered a period of 5 years and 5 months (January 2003-May 2008). Patients who had started thalidomide monotherapy for SRAS during the 2003-2006 period were eligible. Data were collected from patients' medical charts and supplemented by patients' responses during a targeted telephone interview. Ninety-two patients followed at 14 centers were included: 76 had oral or bipolar aphthosis, and 16 had Behçet disease. Thalidomide was rapidly effective: 85% (78/92) entered complete remission (CR) within a median of 14 days. Response time was independent of the initial thalidomide dose (r = 0.04). Thalidomide was continued for > or =3 months (maintenance therapy) by 77/92 (84%) of the patients on 1 of 2 maintenance regimens: continuous therapy with regular intake (60/77) or intermittent therapy in response to attacks (17/77). Although intermittent therapy was less restrictive than continuous therapy, medical supervision under the former was less rigorous. The median maintenance dose was 100 mg/week, and did not reflect the initial dose (r = 0.18). The intermittent-treatment group's median dose was significantly lower and its median duration of thalidomide intake significantly longer than for patients on continuous therapy (19 vs. 150 mg/wk; p < 0.0001, and 32 vs. 19 mo; p = 0.002, respectively). Adverse events were reported by 84% (77/92) of patients. They were mostly mild (78% of patients), but sometimes severe (21%). Nevertheless, after 40 months of follow-up, 60% of patients were still receiving continuous or intermittent maintenance therapy with favorable efficacy/tolerance ratios. Despite its retrospective nature, this detailed study provides novel information on the different ways thalidomide is used as SRAS maintenance therapy in a large and unselected cohort of patients. Low-dose maintenance regimens appear to be widely used, effective, and relatively well tolerated. These observations suggest the value of undertaking a randomized trial to assess various maintenance regimens.

Factors influencing the clinical evaluation of facial acne.

Existing scoring systems for facial acne focus on the lesions themselves, but clinical decisions are based on a general assessment of severity, including the time since onset, the site(s) of involvement, the patient's history, and the response to prior treatments. The aim of this study was to investigate the influence of some of these factors on the global assessment of acne severity. Involvement of the trunk, prior systemic treatment and a positive family history of acne increased the severity score. Inclusion of these factors could help to compose more homogeneous groups for clinical trials.

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.

Lymph nodes in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory disease, and yet palpable lymph nodes are rarely found. This may be due to lack of lymph node swelling or to the inability to palpate lymph node regions due to overlying disease. Ultrasound was used to identify and measure regional lymph nodes in HS patients. METHODS: High-resolution ultrasound scanning was carried out with compact linear 15-7 MHz and linear 12-5 MHz probes in both axillae and inguinal regions following informed consent. RESULTS: A total of 198 lymph nodes were identified in 6 HS patients in Hurley stage II and 4 in stage III, and 101 from regional control scans in healthy controls. All the lymph nodes in both HS patients and controls showed a normal oval shape, with a hypoechoic rim and a hyperechoic center, and all were located in the deep subcutaneous tissue. The overall mean lymph node number per region was not significantly different. The overall mean lymph node diameter was not significantly different, but in patients with Hurley stage III disease it was significantly increased (1.3 +/- 0.4 cm, p = 0.03). CONCLUSION: Lymph node involvement only occurs with late-stage HS and may therefore reflect secondary infection rather than primary etiological involvement.

Creation of a tool to assess adherence to treatments for acne.

BACKGROUND: Acne is a disorder in which adherence has a major impact on treatment outcome. OBJECTIVE: To create an easy-to-use tool to assess treatment adherence, based on a questionnaire that can be used on a daily basis by dermatologists. METHODS: First, we evaluated adherence by comparing responses to a self-administered questionnaire with the dermatologist's prescription. Second, concordance was assessed between adherence and each question of a dermatologist-directed questionnaire (DDQ) administered during the consultation. Third, DDQ questions were combined to construct a mini-questionnaire, and these combinations were tested to maximize specificity. RESULTS: The study included 246 patients, who were prescribed topical treatment alone, combined treatment (excluding oral isotretinoin) or oral isotretinoin alone. The mini-questionnaires for oral and topical treatments had 89% specificity for detecting poor adherence. An inappropriate answer to one question classified the patient as a probable poor compliance. CONCLUSIONS: Our mini-questionnaires provide dermatologists with specific tools to rapidly identify poor compliance.

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.

Minocycline-induced DRESS: evidence for accumulation of the culprit drug.

BACKGROUND: Minocycline-induced drug rash with eosinophilia and systemic symptoms (DRESS) may have a prolonged course, especially in African and African-American patients. OBJECTIVES: To determine if a prolonged course of minocycline-induced DRESS was associated with an accumulation of the culprit drug. PATIENTS AND METHODS: We determined plasma and skin levels of minocycline in patients with minocycline-induced DRESS. We investigated the genetic polymorphisms of enzymes potentially involved in the detoxification of the drug, glutathione S-transferases and UDP-glucuronosyltransferases. RESULTS AND CONCLUSIONS: We demonstrated the persistence of minocycline in the plasma and/or in the skin of 7 out of 9 patients with skin phototypes V-VI. As pigmented skin contains more melanin, this could promote the formation of a melanin-minocycline complex, which could explain the severe and prolonged DRESS which may occur in this subgroup of patients.