Acne is the most frequent reason for seeing a dermatologist, but its physiopathology is not completely well-known. Yet understanding of the mechanisms of action of the different acne treatments is ...very important to optimize their use. A lot of new data on the physiopathology have recently been published in the acne field. This paper summarizes the main points of these new facts.
Every new drug has the potential for causing cutaneous adverse drug reactions. Usually the clinical pattern is well known and has been described in association with other drugs; new entities, ...however, are described frequently. This article reviews several of them.
We studied 11 consecutive patients with classical cicatricial pemphigoid (CP) using direct immunoelectron microscopy (IEM) and Western immunoblotting analysis. Direct IEM performed in the skin or ...gingival mucosa revealed in all 11 CP patients that immunoglobulins and complement deposits were usually thick and discontinuous along the dermoepidermal junction, mostly localized on the lamina densa and occasionally in the lamina lucida. By direct IEM, the ultra-structural aspect in CP differs from the pattern observed in bullous pemphigoid (BP) and from that of chronic epidermolysis bullosa acquisita (EBA). Nine CP patients were studied by Western immunoblotting and, of these nine, only two had detectable anti-basement membrane zone (BMZ) antibodies by indirect immunofluorescence on salt-split skin. By immunoblotting performed on protein extracts of heat-separated epidermis, eight out of the nine CP sera specifically reacted with two protein bands of approximately 230 – 240 kD and 180 kD, similar to those recognized by BP sera in co-migration experiments. By immunoblotting on skin BMZ extracts, none of these nine CP sera recognized the 290-kD major polypeptide of EBA antigen. Taken together, these results suggest that, in CP, the target-antigen, as identified on immunoblots, is similar to BP antigen, but with an abnormal expression within the dermoepidermal junction of patients, which may in part explain the scarring course of the disease.
Lymph nodes in hidradenitis suppurativa Wortsman, Ximena; Revuz, Jean; Jemec, Gregor B E
Dermatology (Basel),
01/2009, Letnik:
219, Številka:
1
Journal Article
Recenzirano
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.
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.
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).
Lymph node involvement only occurs with late-stage HS and may therefore reflect secondary infection rather than primary etiological involvement.
Context:Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. Objective:To evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis. ...Design, Setting and Participants:Randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicentre trial lasting 3 months, and an open-label study from month 3 to month 6. Adults with clinical and histological diagnosis of cutaneous sarcoidosis were included in nine hospital centres in France. Intervention:Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for three 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. Main outcome measures:The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement of 3 target lesions scored for area and infiltration, were compared across randomisation groups. Results:The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients (20%) in the thalidomide group vs 4 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 3 in the placebo group. We observed a large number of adverse event-related discontinuations in patients under thalidomide in the first 3 months (4 patients with thalidomide, 0 with placebo), and in the 3 following months (5 patients). Conclusion:At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis. Trial registration:NCT0030552 (ClinicalTrial.gov). Context: Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. Objective: To evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis. Design, Setting and Participants: Randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicentre trial lasting 3 months, and an open-label study from month 3 to month 6. Adults with clinical and histological diagnosis of cutaneous sarcoidosis were included in nine hospital centres in France. Intervention: Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for three 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. Main outcome measures: The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement of 3 target lesions scored for area and infiltration, were compared across randomisation groups. Results: The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients (20%) in the thalidomide group vs 4 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 3 in the placebo group. We observed a large number of adverse event-related discontinuations in patients under thalidomide in the first 3 months (4 patients with thalidomide, 0 with placebo), and in the 3 following months (5 patients). Conclusion: At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis. Trial registration: NCT0030552 (ClinicalTrial.gov).
Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-α and the balance between the different ...lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.
Minocycline-induced drug rash with eosinophilia and systemic symptoms (DRESS) may have a prolonged course, especially in African and African-American patients.
To determine if a prolonged course of ...minocycline-induced DRESS was associated with an accumulation of the culprit drug.
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.
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.
L’hidradénite suppurée ou maladie de Verneuil (ou « acne inversa ») est fréquente en particulier chez la femme. Elle est souvent méconnue et son diagnostic retardé. Cliniquement elle se traduit par ...des nodules douloureux, des abcès et des cicatrices hypertrophiques en corde présents dans les zones anatomiques riches en glandes apocrines (régions axillaire, inter- ou sous-mammaires, génitale, périanale). Elle se comporte comme une maladie chronique et sévère. Le tabagisme et l’obésité sont des facteurs de risques reconnus, mais la cause de la maladie de Verneuil est inconnue : cette maladie du follicule pileux n’est ni infectieuse, ni hormonale. Les formes graves sont rares. Le retentissement sur la qualité de vie est sévère même dans les formes modérées. Le traitement est médical et chirurgical : antibiotiques à large spectre et exérèses adaptées à l’étendue des lésions. Les agents anti-TNF-α, au rapport risque–bénéfice débattu, et certains lasers sont à l’étude. Elle est parfois associée à une maladie de Crohn. Son cours évolutif peut être émaillé d’un rhumatisme inflammatoire apparenté aux spondylarthropathies avec des formes axiales et des oligoarthrites périphériques rythmées par les poussées de la dermatose.
Hidradenitis suppurativa, or Verneuil's disease, is common, especially in women, but it is often undiagnosed. Clinical manifestations include painful nodules, abscesses, sinus tracts, and rope-like hypertrophic scars in the apocrine gland-bearing areas (axillae, groins, genitals, perianal area). It is a chronic and severe disease. Smoking and obesity are risk factors, but its 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-TNF-α agents are moderately effective; their risk–benefit ratio is still in question. Laser treatment is under study. Spondylarthropathies in the setting of Crohn's disease, as an association, or isolated can also be a diagnostic feature of Verneuil's disease, and can occur during disease flares.
BACKGROUND: It has been proposed that Fas–Fas ligand interaction was responsible for the apoptosis of epidermal cells in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and that ...high doses of intravenous immunoglobulin (IVIG) could help patients by blocking the apoptosis. OBJECTIVE: To study the effects of IVIG on SJS and TEN. DESIGN: Prospective open trial. SETTING: Referral center of a university hospital. PATIENTS: Thirty-four consecutive patients admitted for SJS (n = 9), SJS-TEN (n = 5), or TEN (n = 20) a mean of 4.3 days after onset. INTERVENTION: A dose of 2 g/kg of IVIG was administered within 2 days (half doses or full doses over a longer period for patients with low creatinine clearance). MAIN OUTCOME MEASURES: Detached plus detachable proportions of the total body surface area measured before and after treatment and predicted death rate estimated onadmission with a validated prognostic score. RESULTS: Epidermal detachment involved a mean ± SD 19% ± 16% of the total body surface area on admission and 32% ± 26% after IVIG treatment (progression in 22 of 34 cases, including most patients referred early). The prognostic score predicted 8.2 deaths (24%); 11 were observed (32%; 95% confidence interval, 17%-51%). Most deaths occurred in elderly patients who had initially impaired renal function. CONCLUSIONS: The confidence interval of the observed death rate excludes a dramatic decrease in mortality. No measurable effect was observed on the progression of detachment or on the speed of reepidermalization. These results do not support the routine use of IVIG treatment for patients with SJS or TEN, especially in cases of impaired renal function.
PDF