Christian Beier

Tolerance of fondaparinux in a patient allergic to heparins and other glycosaminoglycans

We here report a 57-year-old Caucasian female patient with a history of DTH to several heparins, who was admitted as an inpatient for treatment of venous ulcers. In the light of her history, the glycosaminoglycan danaparoid (Orgaran) was chosen for prophylactic anticoagulation, which was necessary because of immobility and obesity. Two days after the initial injections, the patient developed erythematous plaques and disseminating papulovesicles at the injection sites (Fig. 1). Assuming DTH to danaparoid, anticoagulation was switched to the low molecular weight selective factor-Xa-inhibitor fondaparinux (Arixtra, Sanofi-Synthelabo, Berlin, Germany; 2.5mg subcutaneously per day), because recent reports document absence of in vitro cross-reactivity with antibodies to heparin-platelet factor 4; these may be associated with allergic heparin-induced skin reactions (2, 3). Fondaparinux was well tolerated throughout the treatment period of 2 weeks. A comprehensive series of skin allergy tests was initiated 6 weeks after clearance of the patient’s skin lesions using undiluted original drugs. Several heparins yielded positive i.c. test results at days 4–8 after injection of 0.1ml (undiluted drug, applied to the inner aspect of the lower left arm) with erythematous plaques developing at the injection sites (Table 1). A therapeutic dose of pentosan polysulfate was also injected subcutaneously, resulting in the formation of a similar lesion. In contrast, all skin tests with fondaparinux remained negative, and re-exposure 4 weeks after termination of the treatment was tolerated by the patient.

Annular leukocytoclastic vasculitis in association with chronic hepatitis B.

Editor A 68-year-old man was admitted to our department with a history of recurrent leucocytoclastic vasculitis over a 12-month period. The patient presented with multiple annular-shaped purpuric lesions on the gluteal region, the trunk and the legs, which measured up to 30 cm in diameter and with unaffected skin in the centre of the lesions (fig. 1). The patient had no fever or other systemic manifestations. Histological examination of skin biopsy specimens revealed leucocytoclastic vasculitis, with typical perivascular neutrophilic and eosinophilic infiltrates and leucocytoclasis. Extensive clinical and laboratory workup revealed a chronic hepatitis B virus (HBV) infection with mixed cryoglobulinaemia, suggesting the presence of HBVrelated cryoglobulinaemic vasculitis. Despite the treatment of the hepatitis B with lamivudine, only symptomatic treatment with dapsone 200 mg/day was seen to successfully ameliorate clinical occurrence of the very seldom annular-shaped leucocytoclastic vasculitis. Leucocytoclastic vasculitis is well characterized by necrotizing neutrophilic inflammation of small dermal blood vessels mainly resulting in palpable purpura. There are many underlying conditions as drugs, infections, malignancies as well as connective tissue diseases provoking a leukocytoclastic vasculitis. Different clinical forms of appearance as for example the papular-necrotic, the polymorphic-nodular or the haemorrhagic type of vasculitis can be distinguished. The annular leucocytoclastic vasculitis is an entity which was first described by Degos and Guiliane in 1962. Up to now, there are about 15 case reports in the English published work describing this very rare disease often associated with systemic ailments as monoclonal gammopathy, sarcoidosis, ulcerative colitis, myelomatosis and one case of pregnancy. Recently, it could be shown, that this kind of vasculitis can even be induced by the analgesic chlorzoxazone. In our case, a clear correlation between chronic hepatitis B with associated mixed cryoglobulinaemia and the appearance of the annular-shaped leucocytoclastic vasculitis could be demonstrated. Cryoglobulins, which are naturally present in very small amounts in the serum, are often strongly elevated in pathological conditions as hepatitis B, C, systemic lupus erythematosus, mycosis fungoides or chronic lymphatic leukaemia and are well-known inducers of leucocytoclastic vasculitis. Interestingly, the most potent treatment for this rare disease seems to be dapsone in a daily concentration between 100 and 200 mg. Up to now, the way of action of this sulphone could not be elucidated, but there is a variety of diseases, as for example pyoderma gangrenousus or herpetiform dermatitis, where the anti-inflammatory and immunosuppressive properties are successfully applied. In our case, only the combination of lamivudine to treat the hepatitis and dapsone 200 mg/day successfully ameliorated the clinical occurrence of the annular leucocytoclastic vasculitis and provoked a long-lasting remission. Thus, this is the first report of the coincidence and the effective treatment of an annular leucocytoclastic vasculitis in association with chronic hepatitis B.

Laser Skin Ablation: An Update on Aesthetic and Medical Indications

Summary The precise and careful tissue removal achievable with the Er:YAG-laser has led to a broad use of this unique and versatile instrument as a device for facial rejuvenation but also in the ablative removal of many superficial skin lesions. While newer nonablative skin rejuvenation techniques as well as the recent introduction of photodynamic rejuvenation have noticeably influenced the concepts of using ablative lasers for resurfacing photoaged skin, there is however a growing awareness on the broad and increasing range of reported indications for laser ablation or laser assisted procedures in diverse other skin disorders.

Suberythrodermic pustular psoriasis induced by clopidogrel

SIR, We report a pustular psoriasis eruption after treatment with clopidogrel, a widely used thrombocytic aggregation inhibitor. A 68-year-old women, who had had psoriasis for more than 37 years, presented with severe suberythrodermic pustular psoriasis. She had no fever or other systemic manifestations and laboratory tests displayed only a slight increase in C-reactive protein and a leucocytosis of 17Æ6 · 10 L. There was no clinical evidence of infection. Skin biopsy showed signs of psoriasis with pustular differentiation and numerous neutrophilic granulocytes (Fig. 1). The eruption could only be linked to a prescription of the angiotensinconverting enzyme (ACE) inhibitor captopril 25 mg once daily and the thrombocytic aggregation inhibitor clopidogrel 75 mg once daily for newly diagnosed coronary heart disease 2 weeks previously. Before starting this new medication our patient had only minimal signs of stable psoriasis. Both medicaments were discontinued on the assumption that the ACE inhibitor had triggered the exacerbation of psoriasis. The patient was treated with a topical coal tar preparation and calcipotriol as well as oral prednisolone and methotrexate. The skin eruption cleared rapidly and after 312 weeks, 2 days before discharge, the patient was re-exposed to clopidogrel because of a known intolerance to acetylsalicylic acid. Within a period of 24 h a new severe eruption of erythrodermic psoriasis occurred and clopidogrel was replaced by the thrombocytic aggregation inhibitor dipyridamole, which was tolerated by the patient and did not provoke new eruptions. Many drugs have been implicated in psoriasiform drug eruptions. Up to now drugs such as b-adrenergic blocking agents, lithium, nonsteroidal anti-inflammatory agents, antimalarial drugs and ACE inhibitors have been found to trigger or aggravate psoriasis. Clopidogrel inhibits platelet aggregation by antagonizing the platelet adenosine diphosphate receptor P2Y12, and is effective in the prevention of vascular events in patients with cerebrovascular or cardiovascular diseases associated with high risk of thrombotic events. The adverse effects of clopidogrel include gastrointestinal problems such as nausea, vomiting, diarrhoea and gastrointestinal haemorrhage and, in some cases, severe rashes such as angio-oedema or hypersensitivity skin rash. To our knowledge, this is the first report of psoriasis induced by clopidogrel. This may have severe consequences for patients with psoriasis and a comorbidity, e.g. coronary heart disease and acetylsalicylic acid intolerance. In our patient, the platelet aggregation inhibitor dipyridamole was a possible alternative medication. Hence, clopidogrel should be added to the list of drugs that may induce or exacerbate psoriasis.

Cutaneous leishmaniasis: Clinical report of two cases and review of the recent literature

With 1–1.5 million cases reported every year cutaneous leishmaniasis represents an increasing health problem. The course of cutaneous leishmaniasis varies from a single self‐healing ulcer to a persistent ulcer or progressive mucosal disease with nasopharyngeal destruction. An enormous array of topical and systemic treatment modalities has been endorsed. The response to treatment depends on the species of parasite as well as the hosts immunological and genetic status. Species‐specific treatment guidelines based on evidence from controlled studies are highly desirable. We present two cases of cutaneous leishmaniasis, one in a child and one during pregnancy, reviewing various diagnostic and therapeutic measures with special attention to problems in young and pregnant patients.

Erbium:YAG Laser Therapy of Skin Lesions

Summary Owing to its high versatility and precision in combination with an extremely tissue sparing skin-ablative work the Er:YAG laser has rapidly been recognized as an ideal tool to treat a large variety of skin disorders. Among others, indications include various epidermal lesions, benign dermal and adnexal tumors, melanocytic disorders, scar revisions, or resurfacing procedures in photodamaged skin. This review article deals with technical aspects of Er:YAG laser use, its preferential use in the field of Dermatology and also with potential hazards and side effects.

Dystrophic calcinosis cutis after subcutaneous administration of para-aminosalicylic acid for treatment of pulmonary tuberculosis

An 81‐year‐old women presented with monstrous subcutaneous mobile masses on the ventral and ventrolateral surfaces of her thighs. Radiography as well as computer tomography showed extensive soft tissue calcifications. We interpreted these alterations as dystrophic calcinosis cutis, most likely resulting from repeated subcutaneous PAS infusions for the treatment of pulmonary tuberculosis.

Kutane Leishmaniose: Zwei Fallberichte mit aktueller Literaturübersicht

Mit einer Inzidenz von 1–1,5 Mio.Neuerkrankungen/Jahr stellt die kutane Leishmaniose (CL) ein zunehmendes gesundheitliches Problem dar. Die CL kann als eine chronische Ulzeration auf die Haut begrenzt bleiben oder sich als mukokutane Form an Haut und Schleimhäuten mit Zerstörung des Nasopharyngx manifestieren. Die Behandlungsmodalitäten umfassen eine Vielzahl an topischen sowie systemischen Therapiemöglichkeiten. Das therapeutische Ansprechen ist abhängig von der jeweiligen Erregerspecies sowie dem immunologischen und genetischen Status des Patienten. Speciesspezifische Therapierichtlinien auf dem Boden von kontrollierten klinischen Studien gewinnen zunehmend an Bedeutung. Im Folgenden berichten wir über ein 2-jähiges Mädchen und eine 21-jährige Schwangere mit einer CL und diskutieren die therapeutischen Möglichkeiten.