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.

[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.

[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.

[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.

Comparison of the DNA damage photoinduced by fenofibrate and ketoprofen, two phototoxic drugs of parent structure.

Fenofibrate and ketoprofen (KP) are two drugs of similar structure derived from that of benzophenone. Both are photoallergic and promote cross reactions in patients. However, the cutaneous photosensitizing properties of KP also include phototoxic effects and are more frequently mentioned. To account for this difference in their in vivo properties, their in vitro photosensitizing properties on DNA were compared. First, it was shown that under irradiation at 313 nm, fenofibric acid (FB), the main metabolite of fenofibrate, photosensitized DNA cleavage by a radical mechanism similar to that proposed for KP but with a 50 times lower efficiency. Furthermore, FB did not photosensitize the formation of pyrimidine dimers into DNA in contrast to KP, which did promote this type of DNA damage. Their difference in efficiency as DNA breakers was compared to their relative photochemical reactivity and the quantum yield of FB photolysis was found to be eightfold lower than that of KP. The reactivity of these drugs cannot explain alone the difference in their photosensitizing properties. Other factors such as the magnitude of the ionic character of the photodecarboxylation pathway of these benzophenone-like drugs are considered in the discussion.

Laser Doppler flowmeter and standardized thermal test in normals and Raynaud's phenomenon.

The diagnosis of Raynaud's phenomenon alone requires clinical investigations. To determine the stage of the disease, its etiology and pathophysiology, it seems desirable to perform noninvasive tests. Conclusions regarding control o the skin or muscle components of hand blood flow rely on evidence from separate measurements of skin or muscle blood flow. We described a standardized thermal provocation test, then respiratory maneuvers and pharmacological trials, to stimulate the microcirculatory control. The total cutaneous blood flow was continuously registered using a laser Doppler flowmeter. We conducted a prospective study on 100 subjects: 21 normal, 22 primary Raynaud's phenomenon (PRP), 26 secondary (SRP), 31 various microcirculatory diseases. The basal blood flow was lower in cases of severe SRP and acrocyanosis. In comparison with normals, RP cases present a less noticeable reaction to cold. Mild SRPs are more sensitive to cold and do not recover during warming up. Severe RPs are less sensitive to cold as they have a lower basal blood flow. Acrocyanosis cases are not sensitive to thermal variations. Post ischemic reactive hyperemia leads to a constant peak flow. Pharmacological assays were performed (nitroglycerine, Nifedipine) during permanent control of skin and muscle blood flow. Laser Doppler and provocation tests have no etiologic value in a Raynaud's phenomenon investigation; this methodology tries to elucidate the pathophysiology, the prognosis and the therapy of Raynaud's phenomenon.

[Value of combining the thermal test with laser Doppler measurement of skin hemodynamics. Study of vascular acrosyndromes]. / Intérêt du couplage du test thermique et de l'hémodynamique cutanée par Doppler au laser. Etude des acrosyndromes vasculaires.

Different exploratory investigations of vascular acrosyndromes have failed to define their physiopathology. Capillaroscopy studies the specific morphologic aspects of certain connective tissue diseases, hemodynamic tests usually determine a global parameter, and those tests investigating cutaneous physiology alone come up against difficulties limiting their diffusion. The laser Doppler flowmeter (LDF) measures global skin flow in a reproducible, continuous simple manner, and was combined with standardized provocation tests during a prospective study to assess its value in angiology. The protocol involved a prospective study of 100 subjects during the winter 1984-1985: 21 healthy volunteers, 11 cases of acrocyanosis, 9 of acrorhigosis, 48 of Raynaud's phenomenon (22 primary and 26 secondary), 11 of connective tissue disease without Raynaud's phenomenon (table I). The LDD test measures skin microcirculation flow continuously in parallel with skin thermometry. Provocation tests included a standardized thermal test (fig. 1); the temperature is automatically reduced to 0 degree C in 15 minutes and then increased to 25 degrees C in 10 minutes in a jar into which the hand and forearm of the patients and any measuring captor are introduced. Respiratory provocation and additional pharmacologic tests were also completed. Interpretation of results involved calculation of the mean skin flow, Dm, pulsatile skin flow, Dp (fig. 2 and 3), at the basal state and then during temperature variations. The reference value of Dm is 2.741 +/- 0.378 V and is decreased in acrorhigosis, acrocyanosis and severe Raynaud's phenomenon. At 0 degrees C the decrease in Dm is 33 +/- 13% in healthy subjects. Specific values for different acrosyndromes and particularly the various types of Raynaud's phenomenon do not exist.(ABSTRACT TRUNCATED AT 250 WORDS)

[Psoriatic acropachydermy]. / Acropachydermie psoriasique.

We report the case of a 55-year old man complaining of painful distal changes in the fingers. At physical examination the distal part of the fingers was enlarged as a result of thickening of the soft parts of the ungueal phalanges, and ungueal dystrophies were present. The patient also had inflammatory arthralgia of the distal interphalangeal (DIP) joints, with limited flexion movements. Interrogation revealed a history of cutaneous psoriasis, and radiography of the hands showed DIP arthritis as well as osteitis and periostitis of the ungueal phalanges. The condition was diagnosed as classical psoriatic arthritis of the DIP type, and psoriatic onycho-pachydermo-periostitis, a new form of psoriatic arthritis recently described by Fournié et al. These authors have put forward a physiopathological hypothesis indicating a direct link between psoriatic inflammatory ungueal lesions and lesions of the ungueal phalanx and its soft parts. We had great difficulty in ascertaining the psoriatic nature of this acropachyderma, and we made successive tentative diagnoses of DIP osteoarthritis, pachydermo-periostitis and acromegaly. In this study, we describe the appearance of the ungueal lesions suggestive of psoriasis, and the other clinical forms of psoriatic arthritis.

[Histopathology of exogenous and idiopathic lucites and provocation phototests]. / Histopathologie des lucites exogénes et idiopathiques et des phototests de provocation.

OBJECTIVE: Provocative phototests are used regularly to explore photobiology in patients with photodermatoses. Our objective was to determine the reliability of the phototest in the diagnosis of idiopathic and exogenous light eruption in order to identify the ideal date for the histological examination by correlation between the histological aspects of light- triggered and spontaneous lesions. PATIENTS AND METHODS: Among 66 patients, there were 48 with polymorphous light eruptions, 13 with exogenous eruptions and 5 with chronic actinodermatitis. The histological findings of the provocative phototests were correlated with the clinical aspect, the date of biopsy and the histological aspect of the spontaneous lesions. RESULTS: In polymorphous light eruptions (48 cases) this test triggered a photoallergic reaction in 48% of the patients. There was a good correlation between the histological findings and clinical features in 96% of the cases. The histological image of the light-triggered lesion on day 6 was the closest to that of the spontaneous lesion. In exogenous eruptions and chronic actinodermatitis (18 cases), only 33% of the clinically positive phototests were also positive at histological examination. The histological image was the same for the provocative tests whether they were clinically positive or negative, with signs of epidermal phototoxicity, regeneration acanthosis and moderate perivascular lymphocyte infiltration of the superficial dermal layer. CONCLUSIONS: Our findings confirmed that the phototest provides a good correlation between histological findings and clinical presentation in idiopathic polymorphous light eruptions, justifying simple clinical interpretation, but did not demonstrate a rate of positive results as high as reported in the literature. Day 6 is the ideal date for a phototest biopsy. In exogenous light eruptions, the phototest is less reliable since the correlation between histology and clinical presentation is weaker. It is difficult to reproduce spontaneous lesions with the phototest, but if used, the phototest biopsy should be done on day 18.

[Systemic sensitization to 17-beta estradiol induced by transcutaneous administration]. / Sensibilisation systémique au 17 beta-oestradiol induite par la voie transcutanée.

INTRODUCTION: Transdermal administration of drugs to obtain a systemic effect may lead to allergic sensitization and compromise subsequent use via another administration route. OBSERVATION: A 52-year-old woman presented contact eczema with the transdermal therapeutic system Estraderm TTS50. Generalized eczema developed later after oral administration of an oestrogen derivative. Skin tests demonstrated allergic sensitization to 17 beta-oestradiol. DISCUSSION: Contact eczema due to transdermal therapeutic systems are usually caused by agents other than the active drug. Sensitization to the active drug raises the risk of generalized eczema and subsequent systemic complications. This risk must be taken into account when prescribing substitution hormone therapy for menopause.

[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.

[Syphilitic labial leucokeratosis]. / Leucokératose labiale syphilitique.

BACKGROUND: Several diagnoses, including syphilis, can be entertained in patients with leukokeratosis of the buccal mucosa. We report a case of labial leucokeratosis which revealed latent syphilis. CASE REPORT: A 36-year-old man with a past history of genital syphilis chancre which have been treated 12 years earlier, developed buccal leucokeratosis with no other clinical manifestation. Histology showed dermal infiltration containing plasma cells, polynuclears and lymphocytes. Blood tests were positive for syphilis. Complementary examinations were unable to detect another localization. Leucokeratosis regressed completely after one injection of Extencilline. There has been no recurrence at one year. DISCUSSION: The clinical and histological presentations of syphilis can mimic different skin diseases. Serodiagnosis alone is significant. Isolated buccal lesions are rarely described in syphilis suggesting serodiagnosis should always be ordered. Whatever the clinical stage of the diseases, serological surveillance after treatment for syphilis is essential.