Topical provocation in fixed drug eruption due to metamizol and naproxen.

The aim of this study was to investigate the usefulness of topical provocation in the diagnosis of metamizol- and naproxen-induced fixed drug eruption (FDE). Five patients with metamizol- and four patients with naproxen-induced FDE established by oral provocation were tested with the causative drugs at concentrations of 10%, 20%, and 50% in white petrolatum both on previously involved and uninvolved skin using the occlusive patch test technique. Additionally, four patients with metamizol- and five patients with naproxen-induced FDE, and 20 healthy controls were tested openly with drug preparations in dimethyl sulfoxide (DMSO). Tape-stripping occlusive patch testing in petrolatum remained negative in all. Open testing with drug preparations in DMSO revealed positive results in all four patients tested with metamizol mainly at concentrations of 20%, and in three of five patients tested with naproxen exclusively at concentrations of 50%. No positive reaction was seen on previously uninvolved skin and in healthy controls with any drug concentration and pure DMSO. In conclusion, repeated open testing with concentrations of the drugs up to 50% in DMSO seems to be a reliable test method in metamizol-induced FDE whereas oral provocation is still the most reliable method for naproxen-induced FDE as false negative results were common when testing topically with naproxen.

Granuloma annulare possibly triggered by antitetanus vaccination.

We report the case of a 6-year-old girl with granuloma annulare (GA) possibly related to antitetanus vaccinations. The first episode occurred 2 months after the girl had been vaccinated but the lesions were not located at the vaccination site. After 1 year of being free of lesions, she had a second episode unrelated to vaccination. After another 6-month lesion-free period, the girl was administered another antitetanus vaccination and a solitary lesion developed at the vaccination site within 3 days. A few lesions developed on her legs in the 2 months following the appearance of the initial plaque. The literature includes two reports of cases with papular lesions limited to the hepatitis B vaccination site, both histopathologically consistent with necrobiotic granuloma, but clinically not suggestive of GA. To the best of our knowledge, GA following antitetanus vaccination and occurring at the vaccination site has not been reported before. Either the trauma alone from the injection or a vaccine-induced immunological reaction might have triggered the necrobiosis of collagen through some unexplained mechanisms.

Fixed drug eruption induced by trimethoprim-sulfamethoxazole: evidence for a link to HLA-A30 B13 Cw6 haplotype.

BACKGROUND: Recent reports indicated a significant association between fixed drug eruption (FDE) and HLA class I antigens. A strong correlation was found between B22 antigen and feprazone-induced FDE. OBJECTIVE: Our aim was to investigate the association between HLA class I antigens and FDE in Turkey, a country where feprazone is not on the market and trimethoprim-sulfamethoxazole is most often the offending drug. METHODS: HLA class I typing was performed by lymphocytotoxicity assay in 67 unrelated patients with FDE, all established by oral provocation. The frequencies are compared with those of 2378 control subjects. RESULTS: Significantly higher (P <.001) frequencies of the A30 antigen and A30 B13 Cw6 haplotype were found in 42 patients with FDE induced by trimethoprim-sulfamethoxazole. HLA-B55 (split of B22) was present exclusively in trimethoprim-sulfamethoxazole-induced FDE, and in higher frequency than in control subjects. CONCLUSION: To our knowledge, ours is the first report indicating a link between A30 B13 Cw6 haplotype and trimethoprim-sulfamethoxazole-induced FDE. In addition, HLA-B22 was increased in patients with FDE caused by a drug other than feprazone.

Drug related clinical pattern in fixed drug eruption.

Fixed drug eruption (FDE) represents a frequent type of drug eruption in Turkey. The aim of this open study is to analyze the clinical features with special emphasize on drug related pattern in our case series. Sixty-four cases with established FDE by oral provocation were clinically evaluated. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common offender for FDE (75%), followed by naproxen sodium (12.5%), dipyrone (9.5%), dimenhydrinate (1.5%) and paracetamol (1.5%). Sensitivity to more than one drug was not observed. Cotrimoxazole-induced FDE was mainly located on male genitalia. Naproxen predominantly affected lips and face whereas dipyrone mainly caused FDE on trunk and extremities. Statistical analysis revealed a significant difference only for dipyrone versus cotrimoxazole over trunk and extremities (p = 0.03). Familial occurrence, symmetrical and asymmetrical nonpigmenting FDE, linear FDE, solitary plaque on the cheek, and "wandering" FDE were unusual findings of cotrimoxazole-induced FDE. Cotrimoxazole was the leading etiological agent in our series. Cotrimoxazole-induced FDE had some rarely or previously unreported features, but a significant relation between drugs and involved areas or clinical pattern could not be established.

The combined occurrence of macular amyloidosis and prurigo nodularis.

The association of prurigo nodularis (PN) and macular amyloidosis (MA) has not been reported before. Although pruritus related frictional trauma is a well-known cause of PN, its role in the development of MA has always been questioned. We herein report two cases with chronic liver disease and iron deficiency who concomitantly developed MA and PN lesions. Pruritus was the preceding factor and both lesions were confined to scratched areas. The association of two otherwise uncommon dermatoses in pruritic patients and their characteristic distribution might indicate an important role for pruritus-induced scratching in the pathogenesis of MA, too.

Pustular psoriasis with a striking linear pattern.

Pustular psoriasis has different clinicomorphologic forms such as generalized, localized (mainly palmoplantar or acral), and annular. There are also few cases with a linear distribution pattern. We report a case of pustular psoriasis with a striking linear distribution probably related to Blaschko's lines. We suggest that linear pattern should also be considered among the morphologic variants of pustular psoriasis.

Topical provocation in 27 cases of cotrimoxazole-induced fixed drug eruption.

The purpose of this study was to investigate the usefulness of topical provocation in the diagnosis of cotrimoxazole-induced fixed-drug eruption (FDE). 27 patients with established cotrimoxazole-induced FDE by oral provocation and 20 healthy controls were tested with drugs at increasing concentrations in white petrolatum and dimethyl sulfoxide (DMSO) both on previously involved and uninvolved skin sites. Tape-stripping occlusive patch testing in petrolatum remained negative in 19 tested patients. Open testing with drug preparations in DMSO revealed positive results in 25 of 27 tested patients. 1 patient showed an additional positive reaction on previously uninvolved skin. Lesions on male genitalia and on face reacted to testing once with 10% or 20% of the suspected drug, whereas repeated testing with concentrations up to 50% was necessary in lesions on trunk & extremities. Open testing with drug preparations in DMSO at concentrations of 10%, 20% and 50% and pure DMSO remained negative in 20 healthy controls. The present study shows that repeated open testing with graded concentrations of the drugs up to 50% in DMSO is a reliable test method in sulfamethoxazole/trimethoprim-induced FDE. Patients and physicians should be aware of the transient irritant reaction to DMSO that is not infrequent, so as to avoid false-positive interpretations.

Annular elastolytic giant cell granuloma: sparing of a burn scar and successful treatment with chloroquine.

Annular elastolytic giant cell granuloma is a rare granulomatous skin disease characterized by phagocytosis of elastic fibres by multinucleated giant cells. Lesions are either solitary or grouped in a few annular patches with elevated borders and central atrophy. Sun-exposed areas are more commonly involved than covered skin. The pathogenesis of the disease is still controversial. We report a 72-year-old fair-skinned woman with unusual clinical findings. An irregularly shaped erythematous plaque covered the entire face, and hundreds of lichenoid papules were present on both sun-exposed and covered areas which gradually evolved into annular lesions of about 0.5-1 cm in diameter. Sparing of an old burn scar and a nearly complete lack of elastic fibres in the scar site were noted, illustrating the presumed importance of dermal elastic tissue in the pathogenesis. The course of the disease is chronic. Several treatments have been tried, with variable success. In our patient, improvement was achieved with chloroquine over a period of 16 weeks.

Intermittent use of topical dimethyl sulfoxide in macular and papular amyloidosis.

BACKGROUND: Severe and therapy-resistant pruritus is the most prominent feature of macular (MA) and lichen (LA) amyloidosis that leads to further amyloid deposition by recurrent frictional trauma to the epidermis. Of the various therapeutic modalities with variable success, the most encouraging and beneficial effect has been observed with topical dimethyl sulfoxide (DMSO) therapy. In a previous study, we achieved marked clinical improvement in nine of 10 patients in a daily treatment regimen over 6-20 weeks, but relapses occurred in the post-treatment follow-up period. The aims of this study are to investigate whether the patients would benefit from intermittent therapy and to determine the optimal application interval of DMSO to maintain the relief of symptoms. METHODS: Thirteen patients with histopathologically verified cutaneous amyloidosis (five MA, two LA and six biphasic) were enrolled in the study. They were treated once daily with a 50 or 100% DMSO solution until pruritus disappeared. Then, DMSO was applied at increasing intervals until the widest effective application interval for maintenance of relief was reached. Patients were regularly followed-up by a scoring system for pruritus, papules, and pigmentation, control biopsies, photographs, blood biochemistry, and side-effects. RESULTS: The mean time required for the disappearance of pruritus was 4.1 weeks. Remarkable flattening of the papules was achieved after an average therapy period of 9 weeks. After a total therapy period of 6.5 months, a nearly 50% remission in pigmentation and >70% flattening of papules were achieved. The widest effective DMSO application interval was 8.6 days. The side-effects of therapy were contact urticaria, desquamation, burning sensation, and garlic-like breath odor, which were more prominent with the higher concentration of DMSO. In interval therapy, side-effects were tolerated more easily than in daily therapy. No reduction of amyloid deposits was revealed in control biopsies. CONCLUSIONS: Locally applied DMSO can break the vicious "pruritus-amyloid deposition-pruritus" cycle in patients with MA and LA. In addition to its daily use, interval therapy seems to maintain this effect and enables patients to tolerate side-effects more easily.

[Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]. / Orale DMSO-Therapie bei 3 Patienten mit Lipoidproteinose. Ergebnisse einer Langzeittherapie.

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.

[Local DMSO treatment of macular and papular amyloidosis]. / Lokale DMSO-Behandlung der makulösen und papulösen Amyloidose.

Macular amyloidosis (MA) and lichen amyloidosus (LA) are the two major variants of the primary cutaneous amyloidoses which present with severe and therapy resistant itching. Various therapeutic modalities such as antihistamines, intralesional injection or topical application of corticosteroids, etretinate, UVB irradiation and dermoabrasion have been employed with variable success. Recently, in a few case reports authors have observed encouraging beneficial clinical effects by using topical dimethyl sulphoxide (DMSO). In our study 10 patients with either MA or LA or biphasic amyloidosis were treated with a 50% solution of DMSO in water. 9 of them showed marked clinical improvement at the end of 6-20 weeks of treatment. Degranulation and depletion of the mast cells by DMSO is the most probable explanation for the rapid improvement of itching beginning within the first week of therapy. Remarkable flattening of the lichenoid papules which was obtained within 11 weeks of treatment is interpreted as a result of the improvement of itching and the related scratch effect. Histological examination after treatment revealed no disappearance of amyloid deposits in the papillary dermis. In the follow-up period relapses of itching and papules were observed. Therefore further studies are needed to find out the optimal procedure of therapy.