Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. Valaciclovir International Zoster Assessment Group (VIZA).

AIM OF THE STUDY: An observational study with valaciclovir was conducted to assess clinical outcome in herpes zoster, especially pain and associated neurological signs and symptoms in relation to a series of demographic and disease characteristics discernible at presentation. The safety and acceptability of valaciclovir for treatment of zoster was assessed in a wide variety of primary care and clinic referral settings. METHODS: In total, 1897 immunocompetent adults with clinically diagnosed, localized acute herpes zoster were enrolled in this international, open-label study of valaciclovir. All subjects received treatment with oral valaciclovir (1000 mg three times daily) for 7 days from entry to the study and were asked to record the presence of zoster-associated pain and abnormal sensations throughout treatment and 6 months' follow-up. They were seen frequently in clinic to verify subjective assessments and for evaluation of rash healing. Safety and tolerability were assessed by adverse event monitoring. RESULTS: Overall, 1191 subjects (63%) were aged > or = 50 years, and 203 (11%) had ophthalmic zoster. Cessation of zoster-associated pain was significantly faster in the younger age group; median times to loss of zoster-associated pain were 23 days and 9 days in the > or = 50 and < 50 years age groups, respectively. Similarly, abnormal sensations resolved significantly more rapidly in the younger subjects; the median duration of abnormal sensations was 31 days in the > or = 50 year olds and 16 days in those aged < 50 years. In cases of ophthalmic zoster, the rate of pain resolution was not different from those with zoster in other dermatomes (median duration of pain 18 vs. 16 days). However, abnormal sensations persisted significantly longer in subjects with ophthalmic zoster than in those with zoster at other sites (47 vs. 22 days). In addition to advancing age, subjects suffering moderate to severe prodromal pain or acute pain during the rash phase were at significantly greater risk of zoster-associated pain and abnormal sensations persisting for longer. Subjects with concomitant neurological disorders were also more likely to develop prolonged abnormal sensations. Valaciclovir treatment was well tolerated, and adverse events were rare and generally mild. CONCLUSION: This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster-associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre-existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.

Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis.

We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1-2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients.

Bullous pyoderma gangrenosum in a patient with myelodysplastic syndrome during granulocyte colony-stimulating factor therapy.

An unusual case of bullous pyoderma gangrenosum in a patient with myelodysplastic syndrome during treatment with granulocyte colony-stimulating factor (G-CSF) is reported. The possible relationship between G-CSF therapy and pyoderma gangrenosum, as well as the beneficial effect of cyclosporin A therapy, is discussed.

Dietary treatment of dermatitis herpetiformis.

Essentially all patients with dermatitis herpetiformis (DH) and dermal granular IgA deposits have a gluten-sensitive enteropathy as seen in coeliac disease. A gluten-free diet would normally restore mucosal morphology within months. The dapsone medication required to suppress the skin lesions could be gradually reduced and/or finally discontinued in most patients if they constantly adhere to the diet. The immunological reactions may also be reduced. The gluten-free diet could thus be successful both concerning manifestations from the skin and the gut. Although well known in dermatological literature, diet therapy in DH has attracted little interest in journals of nutrition. A survey of this causal diet therapy for the disease therefore seems appropriate.

Diagnostically usable skin lesions in Candida septicaemia.

We present three patients with hematological malignancies, all neutropenic and febrile despite broadspectrum antibiotics. They all developed a sparse rash with purpuric maculopapules with a violaceous hue centrally. These skin lesions were associated with systemic Candida infections and responded well to antifungal treatment. They appeared to be a short-cut to the diagnosis of systemic Candida infections for both the hematologist and the dermatologist.

Epidermal Langerhans' cells in chronic eczematous dermatitis of the palms treated with PUVA and UVB.

Epidermal Langerhans' cells (LC) were studied in patients with chronic eczematous dermatitis of the palms. The monoclonal antibodies anti-Leu 6 and anti-HLA-DR were used, and the cells visualized with an immunoperoxidase technique. Increased numbers of LC were found in allergic contact dermatitis as well as in irritant contact dermatitis and hyperkeratotic dermatitis of the palms. The increased number of epidermal LC in lesional skin may facilitate presentation of exogenous or endogenous antigens to activated T-cells. One hand was treated with PUVA or UVB and the other hand served as a non-exposed control. PUVA treatment cleared the dermatitis and the LC number decreased markedly. With UVB treatment clinical improvement was achieved, and a less pronounced decrease in epidermal LC was noticed. There seems to be a crude relationship between the extent of clinical improvement and the reduction in epidermal LC numbers. The change in LC might be a primary event or secondary to a reduction of the inflammatory process.

Thyroid function in patients with pustulosis palmoplantaris.

Fifty consecutive patients (45 women and 5 men) with pustulosis palmoplantaris were evaluated for thyroid disease. Five women had previously had thyroid disorders for which they were receiving thyroxine substitution therapy. Of the other 40 women three had a raised serum concentration of thyroid-stimulating hormone and nine had high concentrations of antibodies against thyroid "microsomal antigen." During a 4-year follow-up hypothyroidism developed in two women with initially raised thyroid-stimulating hormone, and laboratory test results for one woman indicated subclinical hyperthyroidism. Four of nine patients with thyroid abnormality also had evidence of gastric autoimmunity. Of the patients 94% smoked at the onset of pustulosis palmoplantaris compared with 33% in age- and sex-matched healthy controls. The prevalence of thyroid disease in women with pustulosis palmoplantaris was significantly higher than in a comparable population sample of women from the same geographic region. We conclude that patients with pustulosis palmoplantaris should be screened for thyroid disease.

Epidermal Langerhans' cells in patients with pustulosis palmoplantaris treated with etretinate or etretinate + methoxsalen photochemotherapy.

Epidermal Langerhans' cells (LC) were studied in patients with pustulosis palmoplantaris (PPP) by utilizing the monoclonal antibodies anti-Leu6 and anti-HLA-DR in combination with an immunoperoxidase technique. In non-pustular areas of the skin lesions in PPP, an increased number of epidermal LC was found compared with control subjects. No change in LC counts was observed following etretinate monotherapy for 2 weeks. Etretinate was then combined with PUVA treatment of one palm/sole with the contralateral side as a non-UVA exposed control. After 6-12 weeks of etretinate + PUVA treatment the PPP had resolved and the number of epidermal dendritic HLA-DR+ and Leu6+ cells had normalized. On the contralateral side, etretinate treatment induced a marked clinical improvement and a reduction of HLA-DR+ cells. The observation of an increased LC population in active PPP and a reduction during clinical improvement indicates a close relationship between LC and the activity of PPP.

Oesophageal pemphigus vulgaris.

Symptomatic involvement of the oesophageal mucosa by pemphigus vulgaris is rare. We describe 1 patient who was treated with oral steroids during a blistering phase, when epigastric pain developed. Endoscopy revealed multiple ulcerations all over the oesophagus, but gastroduodenal mucosa was normal. The symptoms disappeared following cimetidine for gastro-oesophageal reflux and increase of steroid dosage. When painful symptoms appear from the upper digestive tract during corticosteroid treatment of pemphigus, the possibility of acantholytic involvement of oesophageal mucosa must be kept in mind. Its implication for the dosage of steroids is opposite that in steroid-induced peptic ulcers. Carefully performed upper gastrointestinal tract endoscopy is helpful in these patients.

PUVA, etretinate, and PUVA-etretinate therapy for pustulosis palmoplantaris. A placebo-controlled comparative trial.

Thirty patients with severe pustulosis palmoplantaris completed a placebo-controlled comparative trial. Patients were randomly allocated to placebo or etretinate therapy; after two weeks, psoralen plus long-wave ultraviolet light (PUVA) treatment was instituted on one hand or foot, while the other hand or foot served as an untreated control. Fourteen of 18 hands or feet cleared with the combined treatment, compared with three of 18 with etretinate treatment and three of 12 with PUVA treatment. Follow-up showed a high relapse rate. Treatment of severe pustulosis palmoplantaris must be individualized to minimize short- and long-term side effects.

Circulating immune complexes in untreated psoriasis. A comparison of Raji-cell radioimmunoassay and polymorphonuclear leukocyte phagocytosis.

Three different in vitro assays for the demonstration of circulating immune complexes were compared in 49 patients with psoriasis. Granulocytes from psoriatic subjects contained immune complex-like material in 25 patients (51%). When psoriatic serum was incubated with granulocytes from healthy blood donors, phagocytosed material was found in 18 patients (37%). The Raji-cell assay was only positive in two of 27 subjects (7%). Of the patients 71% tested positively with one of the granulocyte phagocytosis tests. Both tests were positive simultaneously in 16% and negative in 29% of the patients. The pathogenetic significance of the immune complex-like material is unclear.

Identification of basal cell carcinomas by means of monoclonal antibodies C50 and C241.

The monoclonal antibodies C50 and C241 with specificities for the carcinoma-associated carbohydrate structures sialylated Lea and sialosyllactotetraose, respectively, were used in the indirect immunofluorescent test for demonstration of malignant cells in patients with basal cell carcinoma (BCC). Among a total of 36 patients with BCC, 33 were positive with the MAb C50, and 30 with the MAb C241. All of five patients with premalignant conditions were positive with both antibodies, whereas none of 31 control individuals (biopsies from normal skin or from patients with non-malignant conditions) showed a positive reaction. It is suggested that the technique described may provide a convenient tool for evaluation of samples obtained by microscopically controlled surgery of BCC as well as being an adjunct to conventional light microscopy in pathologic-anatomic diagnosis of potentially malignant disease of the skin.