Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study.

BACKGROUND: There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. OBJECTIVE: To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. METHODS: Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. RESULTS: Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. CONCLUSION: This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.

Physicians involved in the care of patients with high risk of skin cancer should be trained regarding sun protection measures: evidence from a cross sectional study.

BACKGROUND: Knowledge, regarding sun protection, is essential to change behaviour and to reduce sun exposure of patients at risk for skin cancer. Patient education regarding appropriate or sun protection measures, is a priority to reduce skin cancer incidence. OBJECTIVE: The aim of this study was to evaluate the knowledge about sun protection and the recommendations given in a population of non-dermatologists physicians involved in the care of patients at high risk of skin cancer. MATERIALS AND METHODS: This study is a cross-sectional study. Physicians were e-mailed an anonymous questionnaire evaluating the knowledge about risk factors for skin cancer, sun protection and about the role of the physician in providing sun protection recommendations. RESULTS: Of the responders, 71.4% considered that the risk of skin cancer of their patients was increased when compared with the general population. All the responders knew that UV-radiations can contribute to induce skin cancers and 71.4% of them declared having adequate knowledge about sun protection measures. A proportion of 64.2% of them declared that they were able to give sun protection advices: using sunscreens (97.8%), wearing covering clothes (95.5%), performing regular medical skin examination (91.1%), to avoid direct sunlight exposure (77.8%), avoiding outdoor activities in the hottest midday hours (73.3%) and practising progressive exposure (44.4%). CONCLUSION: Non-dermatologist physicians reported a correct knowledge of UV-induced skin cancer risk factors. The majority of responders displayed adequate knowledge of sun protection measures and declared providing patients with sun protection recommendation on a regular basis. Several errors persisted.

Intracellular sequestration of amiodarone: role of vacuolar ATPase and macroautophagic transition of the resulting vacuolar cytopathology.

BACKGROUND AND PURPOSE: Tissue deposits of the anti-arrhythmic drug amiodarone are a major source of side effects (skin discoloration, etc.). We addressed the mechanism of the concentration of amiodarone in cells, and characterized the resulting vacuolar cytopathology and its evolution towards macroautophagy. EXPERIMENTAL APPROACH: Sequestration of amiodarone in human cells (macrophages, smooth muscle cells, HEK 293a cells) was evaluated using its violet fluorescence and cytopathology using GFP-conjugated subcellular markers. Autophagic signalling was probed by immunoblotting for the effector protein LC3. A patient biopsy of amiodarone-induced blue-gray skin discoloration was investigated for the presence of macroautophagy (immunofluorescence for LC3). KEY RESULTS: Most of the amiodarone (1-20 microM, 4-24 h) captured by cultured cells (macrophages were most avid) was present in enlarged vacuoles. The specific vacuolar ATPase (V-ATPase) inhibitors, bafilomycin A1 or FR167356, prevented vacuolization and drug uptake. Vacuoles in HEK 293a cells were positive for markers of late endosomes and lysosomes (GFP-Rab7, -CD63) and for an effector of macroautophagy, GFP-LC3. The vacuoles accumulated endogenous LC3 and filled with lipids (Nile red staining) following longer amiodarone treatments (> or =24 h). The electrophoretic mobility of both GFP-LC3 and endogenous LC3 changed, showing activation in response to amiodarone. Paraffin tissue sections of the pigmented skin exhibited granular LC3 accumulation in superficial dermis macrophages. CONCLUSION AND IMPLICATIONS: Vacuolar sequestration of amiodarone occurs at concentrations close to therapeutic levels, is mediated by V-ATPase and evolves towards persistent macroautophagy and phospholipidosis. This cytopathology is not cell type specific, but tissue macrophages appear to be particularly susceptible.

[The prospective multicenter study on standard photopatch tests by the French Society of Photodermatology from 1991-2001]. / Etude prospective multicentrique 1991-2001 de la batterie standard des photopatch-tests de la Société Française de Photodermatologie.

INTRODUCTION: To develop a standard panel of photopatch tests, the French Society of Photodermatology conducted a prospective study from 1991 to 2001 on the frequency of photoallergens encountered in France and on the relevance of the choice of the various photoallergens. PATIENTS AND METHODS: Thirteen photobiology centers participated in the study from 1991 to 1995, and ten centers from 1995 to 2001. A set of 3 samples of photopatch tests was applied on any patient suspected of photoallergy. On Day 2, two sets were irradiated with ultraviolet A (UVA) and total spectrum (DEM 0.75); with the third set being used as control. Readings were made on D3 and D4. RESULTS: Two thousand sixty-seven patients were tested. Eight hundred fifty-six, i.e., 41% exhibited one or several positive tests. In the majority of cases it was a photoallergy (39.7 to 60% of cases) and eczema (29.5 to 45.6%). Photoaggravation was infrequent (7.9 to 10.3%). Cases of phototoxicity were rare. Sesquiterpenic lactones constantly provoked photoallergy, with 12 cases in 10 years. Although phenothiazines were the most photosensitizing allergens up until 1995, they were then overridden by ketoprofen in 1996 with 107 cases of UVA photosensitive reactions (75 cases) and total spectrum (32 cases). These were followed closely by sun screens, benzophenone (notably Eusolex 4360 with 54 pertinent cases of photoallergy) and dibenzoylmethane (with 31 cases due to Eusolex 8020). UVB filters were all potentially photosensitizing but to a lesser degree from 1 to 5 cases). DISCUSSION: Our results differ from those of Anglo-Saxon teams in the appearance of a new photoallergen, ketoprofen, which provoked numerous photosensitivities in both UVA and UVB. This justifies the systematic addition of this substance in our prospective set. Photoallergy was relatively rare, with around 100 cases reported within 10 years. Total spectrum irradiation of the photopatch tests revealed photoallergies that would not have been found with UVA alone. CONCLUSION: Study of photopatch tests has permitted the uniformization of the methodology in France, an overview of the frequency of the photoallergens tested and the development of a new standard set.

[Worsening of subacute lupus erythematosus induced by infliximab]. / Aggravation d'un lupus érythémateux subaigu sous infliximab.

BACKGROUND: Infliximab (Remicade) is an anti-TNF alpha indicated in the treatment of chronic inflammatory rheumatism, notably rheumatoid arthritis. CASE-REPORT: We report the case of a 56 year-old woman who developed severe worsening of an SSA-positive subacute lupus erythematosus on initiation of treatment with infliximab for rheumatoid arthritis. DISCUSSION: A review of the literature found 30 cases of drug-induced lupus and listed the autoimmune modifications induced by anti-TNF alpha. This first case of subacute lupus erythematosus, existing before the introduction of treatment and worsening during the latter, emphasizes the risk of developing a severe flare of an autoimmune disease during treatment with anti-TNF alpha. It raises the question of the relative contraindications of anti-TNF alpha in patients with lupus erythematosus.

[Nodules on localized scleroderma or morphea]. / Nodules sur sclérodermie en plaque ou morphée.

BACKGROUND: Localized scleroderma or morphea usually appears as flat or depressed lesions. OBSERVATIONS: We report 3 cases of morphea with atypical appearance, alternating pigmented and depigmented patches with nodules or sclerous bands, occurring in adult men. DISCUSSION: The occurrence of nodular elements on generalized or localized scleroderma, although rare, was first reported in the literature by Addisson in 1884. These nodules usually appear during evolution. These scleroderma are then described as being keloidal or nodular. We report 3 cases of nodules on localized scleroderma which appeared at the beginning of the dermatosis and where the scleroderma had a similar unusual irregularly pigmented appearance.

Lupus-like phototriggering in a young woman with benign summer light eruption.

We report the case of a young woman with a single history of benign summer light eruption (BSLE) who developed delayed onset annular lupus-like lesions triggered by a polychromatic phototest, 6 weeks after the irradiation. BSLE of French authors is an idiopathic photodermatosis that corresponds to the minor form of polymorphic light eruption (PLE) of Anglo-Saxon authors. This patient may develop a true lupus erythematosus in the future as indicated by this lupus-like phototriggering and in view of the high prevalence of PLE in lupus patients.

Fixed solar urticaria to visible light successfully treated with fexofenadine.

Fixed solar urticaria (FSU) represents an uncommon form of urticaria related mostly to radiation from the ultraviolet (UVB, UVA) and visible spectrum. The exact pathomechanism has so far remained unknown. A 52-year-old woman with a 3-year history of urticated eruptions limited to certain skin areas is presented. Photobiological testing revealed positive reactions limited to the visible light range. The induced lesions appeared only in originally affected skin sites. The particular distribution of whealing supports the concept of specific alteration of mast cells in well defined areas. The clinical findings and the results of phototesting lead to the diagnosis of FSU to visible light. It is recommended to carry out phototesting in patients with FSU in the originally affected skin areas, usually covered and protected by the patient, to avoid false-negative results. Fexofenadine given in the conventional dosage can prevent recurrences and represents a successful treatment measure when dealing with this peculiar form of solar urticaria.

[Photoaggravated contact allergy and contact photoallergy caused by ketoprofen: 19 cases]. / Allergies de contact photoaggravées et photoallergies de contact au kétoprofène: 19 cas.

INTRODUCTION: Between September 1994 and September 1999, we observed 19 cases of photoaggraved contact allergy or contact photoallergy to ketoprofen (non steroidal anti-inflammatory derived from arylpropionic acid). We present a clinical and photobiological retrospective study of these 19 cases with investigation of cross-reactivity between benzophenone-containing molecules. PATIENTS AND METHODS: On clinical level, we investigated the type of eruption, the delay of appearance, the initial area of eruption and areas of diffusion. Phototesting included patchtests and photopatchtests performed with the gel containing ketoprofen (17 patients), ketoprofen 2 p. 100 petrolatum (14 patients), fenofibrate 10 p. 100 petrolatum and 10 p. 100 water (15 patients), 3 benzophenones (19 patients): oxybenzone 10 p. 100 petrolatum, mexenone 2 p. 100 petrolatum, sulisobenzone 10 p. 100 petrolatum and the other arylpropionic derivatives (4 patients). Three identical series were applied: one was irradiated with 3/4 polychromatic minimal erythematosus dose, a second was irradiated with UVA 13 J/cm2 until January 1997, then 5 J/cm2, the third series was not irradiated (control series). RESULTS: Patients were 9 men and 10 women with an average age of 41.2 years. The type of eruption was an eczema. The delay of appearance of the eruption was one day to 3 months. For 10 patients, the delay was between 4 and 18 days. The eruption was localized to the application area in 1 case, to the application area then to the same contralateral area in 3 cases, to the application area then to all photoexposed areas in 13 cases, to the application area then to the photoexposed areas and then to non-sun-exposed areas in 2 cases. Evolution showed prolonged photosensitivity in 3 cases after withdrawal of the contact and the contact photoallergy to ketoprofen was severe. Gel-containing ketoprofen photopatchtests showed 9 photoaggravated contact allergy, 6 contact photoallergy and 2 contact allergy. Ketoprofen photopatchtests showed 12 contact photoallergy and 2 photoaggraved contact allergy. Tiaprofenic acid photopatchtests were positive in all performed cases (4/4), but photopatchtests with the other arylpropionic derivatives, without benzophenone structure, were negative. Fenofibrate photopatchtests were always positive (15/15). Benzophenones photopatchtests only showed 4 cases of contact photoallergy to oxybenzone (4/19). In 68 p. 100 of cases, patients presented a contact allergy or photoallergy to fragrances. CONCLUSIONS: This study shows the actual frequency of contact allergy and contact photoallergy to ketoprofen with a higher frequency of contact photoallergy. Thus, photopatchtesting is essential. In cases of contact photoallergy to ketoprofen, ketoprofen, tiaprofenic acid but not the other arylpropionic derivatives, fenofibrate and benzophenones have to be withdrawn.

Prolonged photosensitivity following contact photoallergy to ketoprofen.

We report the third case of prolonged photosensitivity secondary to contact photoallergy to topical ketoprofen, a 2-arylpropionic acid derivative. The patient suffered from persistent photosensitivity for more than 1 year after the withdrawal of ketoprofen with recurrent eruptions on sun-exposed skin areas. This photosensitivity was associated with a persistent decrease in polychromatic and UVA minimal erythemal doses. Photobiological testing revealed cross-reactivity with fenofibrate and benzophenones. Photoallergy to ketoprofen is due to the benzophenone structure or to the very similar thiophene phenylketone of tiaprofenic acid, but not to the arylpropionic function. Thus, fenofibrate, tiaprofenic acid and benzophenones should be avoided by patients with a positive history of photocontact dermatitis to ketoprofen.