Langerhans cell histiocytosis: a multisystem disorder.

Langerhans cell histiocytosis can involve single or multiple organ/tissue systems and may go undiagnosed for years until it enters the clinician's differential diagnosis framework. We report on a young patient who initially presented with diabetes insipidus and subsequently with pyrexia of unknown origin. She progressed from single system Langerhans cell histiocytosis to multisystem involvement and remains in long-term remission following chemotherapy.

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit.

BACKGROUND: There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV). OBJECTIVES: To conduct a multicentre case note review to examine real-life management of ELPV comparing current U.K. practice against an agreed audit standard. METHODS: Criteria for standards of care for which to evaluate current service provision were set following communication with experts from the British Society for the Study of Vulval Disease. Participants from 10 U.K. centres included nine dermatologists and one gynaecologist who run specialist vulval clinics. Standards examined the documentation of disease severity/impact measures, the use of diagnostic biopsies, treatments used and assessment of treatment response. RESULTS: Audit data were collected from 172 patients. Documentation of symptoms/clinical findings was excellent (99%, 170/172). A schematic diagram was present in the notes of 87% (150/172). Patient-related disease impact measures including Dermatology Life Quality Index (3%, 6/172) or visual analogue scales (1%, 2/172) were less well documented. Biopsies were performed in 78% (135/172); 71% (96/135) showed histological features consistent with erosive lichen planus. Squamous cell carcinoma developed in four patients (two vulval, two oral) and vulval intraepithelial neoplasia in two further patients. Recommended first-line treatment with a very potent topical steroid was used in 75% (129/172) with improvement in 66% (85/129). Significant variation in second-line therapy was seen. CONCLUSIONS: Wide variation in U.K. practice demonstrates the absence of standardized guidance for treating ELPV and the need for vulval-specific outcomes. This audit should act as a framework towards improving ELPV management and to plan future research in this area.

A retrospective study of post-mortem examination findings in takahe (Porphyrio hochstetteri).

AIMS: To identify the major diseases or disease processes affecting both captive and wild populations of takahe (Porphyrio hochstetteri) in birds submitted for post-mortem examination between 1992 and 2007, and to survey archived wild dead takahe for the presence of Erysipelothrix rhusiopathiae. METHODS: Reports of 199 post-mortem examinations submitted between 1992 and 2007 were reviewed retrospectively. The reports comprised 56 eggs, 51 chicks up to 6 months of age, 13 sub-adults 6-18 months old, 74 adults and five birds where age was not recorded. Bone marrow flushed from the keel of 34 frozen adult takahe was assayed for the presence of E. rhusiopathiae, using PCR analysis. RESULTS: Of the eggs examined, 6/56 (11%) had no recorded diagnosis, 24/56 (43%) were infertile and 26/56 (46%) showed embryonic mortality at various stages. Excluding eggs, the cause of death could not be determined in 64/138 (46%) birds with a recorded age that were examined. Contributing factors for the low rate of diagnosis included advanced decomposition of many carcasses, the freezing of some birds prior to pathological investigation, long delays between recovery and submission for post-mortem examination, and variation in the extent of post-mortem examination and ancillary diagnostic testing. Common post-mortem examination findings in chicks included those related to cardiac disease [11/51 (22%)], infectious or inflammatory disease [9/51 (18%)] and trauma [7/51 (14%)]. In adult birds, the most common post-mortem examination findings were due to infectious or inflammatory disease [15/74 (20%)] including septicaemia due to E. rhusiopathiae [3/74 (7%)], followed by degenerative conditions due to diet, age and husbandry [9/74 (12%)]. Bacteria implicated in the causes of death included Escherichia coli, E. rhusiopathiae, Salmonella enterica serovar Typhimurium, and Pseudomonas aeruginosa. Only 1/34 (3%) of the frozen carcass examined using PCR was positive for E. rhusiopathiae. CONCLUSIONS: This study highlights a need for improved recovery, storage and submission of dead takahe for pathological examination; consistency in post-mortem examination, ancillary testing and recording of findings; and finally, regular communication between wildlife pathologists, conservation workers and representatives of Ngai Tahu.

Guidelines for the management of vulvodynia.

These guidelines for the management of vulvodynia have been prepared by the British Society for the Study of Vulval Diseases Guideline Group. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines.

A comparison of molecular and enzyme-based assays for the detection of thiopurine methyltransferase mutations.

S-Methylation by thiopurine methyltransferase (TPMT) is an important route of metabolism for the thiopurine drugs. About one in 300 individuals are homozygous for a TPMT mutation associated with very low enzyme activity and severe myelosuppression if treated with standard doses of drug. To validate the use of molecular genetic techniques for the detection of TPMT deficiency, we have determined red blood cell TPMT activity in 240 adult blood donors and 55 normal children. Genotype was determined by restriction fragment length analysis of polymerase chain reaction products in a cohort of 79 of the blood donors and five cases of azathioprine-induced myelosupression, and this confirmed a close relationship between genotype and phenotype. In 17 of the 24 cases in which mutations were found, DNA was also available from remission bone marrow. In one of these cases, DNA from the remission marrow sample indicated the presence of a non-mutated allele that had not been seen in the blast DNA sample obtained at presentation. These results indicate that polymerase chain reaction-based assays give reliable and robust results for the detection of TPMT deficiency, but that caution should be exercised in relying exclusively on DNA obtained from lymphoblasts in childhood leukaemia.

An indolent penile herpetic ulcer in a patient with previously undiagnosed human immunodeficiency virus infection.

We report a case of an atypical penile herpetic ulcer in a man with previously undiagnosed human immunodeficiency virus (HIV) infection. Swabs of the lesion were negative for herpes simplex virus (HSV) by culture and electron microscopy. However, histopathology of biopsy material showed characteristic herpetic multinucleate giant cells. Immunochemistry using polyclonal antibodies was positive for HSV1 and HSV2. The lesion completely resolved after treatment with aciclovir and the patient subsequently tested positively for HIV antibodies.

Patch testing with a combination of unrelated allergens: a new strategy.

A simplified method of patch testing was designed, in which several totally unrelated allergens were combined in each patch. The method was evaluated by double blind comparison of responses to 17 standard allergens applied individually as 17 conventional patch tests, and as two different sets of five patches each containing combinations of three of four allergens per patch, in 137 patients under investigation for contact allergic dermatitis. There were 89 positive responses to conventional patch testing with separate allergens and 94 and 86 positives to the two different combinations of the same allergens. Concordance of positive reactions to the two combinations was 80% and there were no irritant reactions. Conventional testing detected 70 and 74% of reactions to combination patches 1 and 2 and combination patches 1 and 2 detected 80 and 79% of the reactions to conventional testing. The combinations detected clinically relevant sensitivities not found by conventional testing. Thus, combination patch testing appears to give consistent and reliable results; its use would reduce the number of patches and increase the diagnostic yield for the specialist and permit preliminary screening by the general practitioner.

Metastatic Crohn's disease of the umbilicus.

We report a case of metastatic Crohn's disease of the umbilicus which responded to topical corticosteroid treatment. Crohn's disease is a granulomatous disease of the bowel which may affect other organs. The skin is commonly involved, and the cutaneous manifestations may be non-specific, e.g. pyoderma gangrenosum or erythema nodosum, or specific with epithelioid granulomas and multinucleated giant cells in the skin. Specific skin lesions may be contiguous with the bowel at sites including the perineum, mouth and adjacent to fistulae, or separated from it by normal skin from the bowel, a rare condition which has been termed 'metastatic' Crohn's disease.

Quantification of contact allergic inflammation: a comparison of existing methods with a scanning laser Doppler velocimeter.

Responses to a range of doses of common contact dermatitis-producing allergens were measured using a novel scanning laser Doppler velocimeter and three commonly used conventional measurement techniques. The techniques were compared in terms of sensitivity, measurement error, range of the linear portion of the dose-response curve and ease of use. The detection thresholds of the objective methods did not differ significantly and did not detect responses at concentrations less than those required to produce a visible response. Of the objective methods the range of linearity was greatest when reactions were measured using change in skin fold thickness, erythema or area of inflammation. Measurement error was greatest with measurements made using the conventional laser Doppler velocimeter. Present instrumental methods are no more sensitive than visual assessment in the reading of patch test reactions. The conventional laser Doppler velocimeter was least suited for measurement of allergic contact hypersensitivity reactions as readings are time-consuming, show detectable changes over a more limited range of allergen concentration, and have a larger measurement error than the other methods. There is no single best method for measuring allergic contact hypersensitivity reactions. Useful data over a wide range of allergen concentrations can best be obtained by measurement of skin fold thickness, erythema or area of reaction using the scanning laser Doppler velocimeter. The scanning laser Doppler velocimeter has the added advantages of being able to measure area of reaction without contact with the skin surface and to measure reactions at all skin sites.

Topical ketoconazole does not potentiate oral cyclosporin A in allergic contact dermatitis.

Cyclosporin A is an effective drug but its use is limited by its side effects. Since oral ketoconazole inhibits the metabolism of oral cyclosporin, we set out to find out whether topical ketoconazole would enhance the effect in the skin of oral cyclosporin. Five patients with contact allergic dermatitis (CAD) were given a 6-day course of cyclosporin (1 mg/kg/day) and applied 2% ketoconazole cream to an area on one arm and the inert base to the other. Serial dilutions of the relevant allergen were applied to the arms at 3 days for 48 hours, and the responses were measured objectively a day later. There was no significant difference between responses at the two sites, indicating that topical ketoconazole does not enable the dose of oral cyclosporin to be reduced in CAD.