C.B. Bunker

Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon

Skin biopsy samples from the fingers of nine patients with primary Raynauds phenomenon, nine with the disorder associated with systemic sclerosis, and eleven healthy controls were examined by immunocytochemistry. There were no differences between the groups in the distribution of PGP 9.5 (a pan-neuronal marker) immunoreactivity, but there was a significant reduction in the number of calcitonin gene-related peptide (CGRP) immunoreactive neurons in the skin of patients with primary Raynauds phenomenon and those with systemic sclerosis. These findings implicate dysfunction of the CGRP neurovascular axis in the pathophysiology of Raynauds phenomenon.

Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases.

Summary Background  Penile intraepithelial neoplasia (PIN) is the term used to describe erythroplasia of Queyrat (EQ), Bowens disease (BD) and bowenoid papulosis (BP). These conditions are distinct clinical entities and have different epidemiological and aetiological associations and prognostic implications.

HLA-C and guttate psoriasis

Background Psoriasis is a heterogeneous disease in its clinical expression. Both genetic and environmental factors are thought to contribute to the pathogenesis of the inflammatory and hyperproliferative components of the typical skin lesions. Predisposing genetic influences include associations with human leucocyte antigens (HLA) of which that with HLA‐Cw6 is the strongest. Guttate psoriasis is a specific clinical manifestation of psoriasis frequently associated with group A β‐haemolytic streptococcal throat infection.

Calcitonin gene-related peptide in treatment of severe peripheral vascular insufficiency in Raynaud's phenomenon

Calcitonin gene-related peptide (CGRP) is a potent vasodilator that may be involved in the regulation of the peripheral circulation and in its response to cold. There is evidence that CGRP in digital cutaneous perivascular nerves is deficient in Raynauds phenomenon. Our pilot study of intravenous CGRP suggested that this substance is beneficial in patients with Raynauds phenomenon; here we have extended our studies. Ten patients with severe Raynauds phenomenon secondary to connective tissue disease were randomly assigned to groups receiving intravenous CGRP (0.6 micrograms/min for 3 h per day on 5 days) or saline. Hand and digital blood flow and skin temperature were measured by thermocouple and laser doppler flowmetry. Blood flow was significantly (p < 0.05) increased by CGRP in both hands (median blood flow after infusion as percentage of baseline reading 179 [range 100-355]%) and fingers (149 [100-161]%); saline had no effect (hands 102 [84-123]%, fingers 96 [81-113]%). Hand temperature was increased more by CGRP than by saline (2.8 [1.5-4.0] vs 1.0 [-1.0 to 2.5] degrees C, p < 0.05). Digital temperature increased after CGRP but the difference between the treatment groups in temperature rise was not significant, perhaps because saline caused increases in some patients. All ulcers healed in four of five CGRP-treated patients but in no saline-treated patients. Thus intravenous CGRP effectively dilates the compromised digital cutaneous vasculature in severe Raynauds phenomenon.

Clinical parameters in male genital lichen sclerosus: a case series of 329 patients

Background  The dermatological aspects of male genital lichen sclerosus (MGLSc) have not received much prominence in the literature. Sexual morbidity appears under‐appreciated, the role of histology is unclear, the relative places of topical medical treatment and circumcision are not established, the prognosis for sexual function, urinary function and penis cancer is uncertain and the pathogenesis has not been specifically studied although autoimmunity (as in women) and HPV infection have been mooted.

Most women with acne have polycystic ovaries

Out of 98 female referrals with acne vulgaris it was possible to define ovarian morphology by high resolution ultrasound imaging of the pelvis in 82 (84%). Sixty‐eight (83%) were shown to have polycystic ovaries, compared with 19% in a control group without acne. The presence of polycystic ovaries in the acne patients did not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinological abnormalities.

Rosai–Dorfman disease complicated by autoimmune haemolytic anaemia: case report and review of a multisystem disease with cutaneous infiltrates

We report a patient with sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) who presented with widespread nodal and extranodal involvement affecting the skin, orbits and nasal sinuses, complicated by the development of autoimmune haemolytic anaemia. The aetiology and pathogenesis of this multisystem disorder are unknown but are thought to represent a reactive histiocytic process to an infective agent rather than a neoplastic or other primary condition. Prognosis is generally good but clinical or laboratory evidence of immune dysfunction tends to predict a poorer outcome. We describe the clinical course of the patient and review the literature on this disease.

HLA-Cw*0602 and HIV-associated psoriasis.

The aetiopathogenesis of psoriasis is unknown, but genetic and environmental factors may be involved. Psoriasis may not be one disease but a cutaneous inflammatory reaction pattern consequent upon several different independent or related stimuli in susceptible individuals. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4 vs. CD8 T lymphocytes. Psoriasis has been associated with HLA-Cw6 and Cw7 by serology and specifically with HLA-Cw*0602 by polymerase chain reaction (PCR) typing. Psoriasis is probably no more common in HIV infection than in the general population; however, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. We have investigated the prevalence of HLA-C alleles, in the specific clinical context of HIV infection complicated by type 1 psoriasis, in a case control study of 14 men with HIV disease and type 1 psoriasis and 147 HIV-infected patients without psoriasis. Typing was performed using PCR with sequence-specific amplification primers. Eleven of 14 patients (79%) with psoriasis carried the HLA-Cw*0602 allele compared with 24.5% of those without psoriasis (odds ratio = 11.31; 95% confidence limits 2. 73 to 65.36; P = 0.0001). Two patients without the HLA-Cw*0602 allele carried instead the closely related Cw*0401/3 allele. The results confirm the previously reported association between the HLA-Cw*0602 allele and type 1 psoriasis, and suggest that the association with HLA-Cw*0602 is stronger in HIV-associated psoriasis although this trend needs to be supported by a larger sample. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. As CD8 T cells recognize antigens in the context of class I major histocompatibility complex, the identification of an HLA class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8 + T lymphocytes in the immunopathogenesis of psoriasis. Investigations of the pathogenesis of psoriasis should take account of clinical and other subtypes already identified.

Evaluation of a novel broad-spectrum PCR-multiplex genotyping assay for identification of cutaneous wart-associated human papillomavirus types

ABSTRACT A large number of human papillomavirus (HPV) types, distributed over five papillomavirus genera, are detectable in the skin. HPV types belonging to the alpha, gamma, and mu genera have been detected in cutaneous warts. A state-of-the-art HPV genotyping assay for these cutaneous wart-associated HPV types does not exist although warts constitute a highly prevalent skin condition, especially in children (33%) and organ transplant recipients (45%). Cutaneous warts are again the focus of attention as their clinical relevance rises with the increasing number of chronically immunosuppressed patients. The objective of this study was to develop and evaluate a DNA-based genotyping system for all known cutaneous wart-related HPV types using PCR and Luminex xMAP technology. The broad-spectrum PCR amplified DNA of all known wart-associated HPV types from the genera alpha (HPVs 2, 3, 7, 10, 27, 28, 29, 40, 43, 57, 77, 91, and 94), gamma (HPVs 4, 65, 95, 48, 50, 60, and 88), mu (HPVs 1 and 63), and nu (HPV41). The probes were evaluated using plasmid HPV DNA and a panel of 45 previously characterized cutaneous wart biopsy specimens showing high specificity. HPV was also identified in 96% of 100 swabs from nongenital cutaneous warts. HPV types 1, 2, 27, and 57 were the most prevalent HPV types detected in 89% of the swabs. In conclusion, this Luminex-based genotyping system identifies all known cutaneous wart HPV types including phylogenetically related types, is highly HPV type specific, and is suitable for large-scale epidemiological studies.

Isotretinoin in the treatment of systemic sclerosis

Thirteen patients with systemic sclerosis were treated with isotretinoin. Nine patients completed between 6 and 14 months of treatment and all showed an improvement in the cutaneous manifestations of their disease. The drug did not appear to benefit internal organs affected by the disease. Most patients experienced the well‐recognized side‐effects of retinoids, which in three cases necessitated withdrawal from the study within 3 months. Serum levels of type III procollagen aminopropeptide did not show a consistent decline during treatment, despite a clinical improvement. The mode of action of the reported therapeutic effect of isotretinoin in systemic sclerosis is unclear. There may be a preferential suppression of the synthesis of type I collagen, or the drug may be acting by an unrelated mechanism.