Susan Burge

Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease

Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2+ -ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca2+-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.

Darier’s Disease

Darier’s disease is a rare cutaneous disease with an autosomal dominant mode of inheritance. Greasy papules and plaques arise on the seborrheic areas and in the flexures and almost all patients have nail abnormalities. Acantholysis and dyskeratosis are the typical histological findings. The underlying defect is a result of mutations in the ATP2A2 gene on chromosome 12q23-24 that encodes for a sarco/endoplasmic reticulum calcium ATPase (SERCA 2). Acantholysis is thought to result from desmosome breakdown. Darier’s disease is an example of a dominantly inherited disease caused by haplo-insufficiency. Oral retinoids are the most effective treatment but their adverse effects are troublesome. Topical retinoids, topical corticosteroids, surgery, and laser surgery have their advocates but evidence for efficacy is sparse.

What should undergraduate medical students know about psoriasis? Involving patients in curriculum development: modified Delphi technique

Abstract Objective To identify the content of a psoriasis curriculum for medical students. Design Literature review and modified Delphi technique. Setting Primary and secondary care in Oxfordshire and Buckinghamshire. Subjects 19 dermatologists (7 teaching hospital consultants; 6 consultants in district general hospitals; 6 registrars); 2 general practitioner senior house officers working in dermatology, 5 dermatology nurses, 7 rheumatologists, 25 general practitioner tutors, and 25 patients with chronic psoriasis. Main outcome measures Percentage of agreement by participants to items derived from literature and our existing psoriasis syllabus. Results 71 (84.5%) of 84 questionnaires were returned. A 75% level of consensus was reached on key items that focused on the common presentations of psoriasis, impact, management, and communication skills. Students should be aware of the psychosocial impact of psoriasis, examine the skin while showing sensitivity, and be able to explain psoriasis to patients in a way that enables patients to explain the condition to others. Conclusions The panels identified the important items for a psoriasis curriculum. The views of patients were particularly helpful, and we encourage educators to involve patients with chronic diseases in developing curriculums in the future. The method and results could be generalised to curriculum development in chronic disease.

The effect of hormonal changes on cutaneous disease in lupus erythematosus.

Summary The behaviour of cutaneous disease in systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE), under the influence of various hormonal states, was studied in 68 patients. In 28 pregnancies, cutaneous disease was essentially unchanged. In a total of 57 patients whose lupus erythematosus (LE) had been diagnosed prior to the menopause, 20% described a premenstrual cutaneous exacerbation. Only three patients had taken an oestrogen‐containing contraceptive. The duration of oral contraceptive treatment before the onset of lupus varied: 1 month in a patient presenting with the acute malar rash of SLE, 2 months in a patient who presented with annular weals and later developed systemic features, and 12 months in a patient who developed generalized DLE. Thirty‐three patients were menopausal at the time of the study; 4% had noticed a perimenopausal cutaneous flare. There was no deterioration in the skin of the five patients on hormone replacement therapy.

The neuropsychiatric phenotype in Darier disease

Background  Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co‐occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain.

Teaching dermatology to medical students: a survey of current practice in the U.K.

Summary Background  In 1993, the General Medical Council recommended that all medical schools should revise their curricula for undergraduate medical education and foster more interdisciplinary collaboration in teaching. In accordance with these recommendations, new curricula have been introduced in U.K. medical schools.

Audit of dermatological content of U.K. undergraduate curricula.

Background  Recommendations for the dermatology content (learning outcomes) of the core undergraduate curriculum were sent to all U.K. medical schools in June 2006.

Grover's disease, despite histological similarity to Darier's disease, does not share an abnormality in the ATP2A2 gene.

Sir, Epidermal grafting with suction blisters is used in treatment of stable vitiligo. Previous reports have shown various complications including postinflammatory hyperpigmentation, peripheral hypopigmentation and hypertrophic scarring. However, the risk of infection has not been reported to date. We report an unusual case of verruca vulgaris that appeared after epidermal grafting. It seems likely that virus particles might have been transferred from the operator, who had verruca vulgaris on his hand, to the patient during the surgical procedure. A 12-year-old girl with localized stable vitiligo was treated by epidermal grafting. Blisters on the recipient site formed within 24 h after three freeze±thaw cycles with liquid nitrogen. Blisters on the donor site were made by suction on the inner portion of the thigh. After approximately 3 h of suction at 200 mmHg, large unilocular bullae appeared. After removal of the blisters at the recipient site, the epidermal sheets were grafted to the denuded recipient site and held in place. Two weeks after grafting, once weekly systemic psoralen-ultraviolet A treatment was started. Almost complete repigmentation was observed 3 months after grafting. Four months after grafting, the patient noticed two verrucous plaques in the grafted site (Fig. 1). She denied warts on any other body sites. There was no history of similar lesions in her family or close friends. The operator, who wore gloves, had a verrucous papule on his hand during the surgery. Skin biopsy of two different lesions, on the patients back and the operators hand, demonstrated histological features of verruca vulgaris. Human papillomavirus (HPV) typing was not performed. Although epidermal grafting appears to be an effective and safe method for the treatment of vitiligo, various complications have been reported, of which some are associated with the application of liquid nitrogen, such as postinflammatory hyperpigmentation, hypertrophic scarring, peripheral hypopigmentation and uneven pigmentation. Koebner phenomenon and recurrence have also been considered complications of epidermal grafting. The possibility of transmission of virus from patient to patient or from patient to doctor has been reported. One study showed that virus may survive on a cotton swab dipped into liquid nitrogen and suggested that virus transmission from patient to patient may occur via this route. Charles and Sire reported the possibility of transmission of papovavirus indirectly by cotton-tipped applicators which had been used earlier to treat verruca in other patients. In our case, the same liquid nitrogen and cotton-tipped applicators were not used for multiple patients. Bergbrant et al. reported that there is a risk of contamination of the operator by HPV DNA, during both carbon dioxide laser and electrocoagulation treatment. Once an individual has been infected, new warts may develop in sites of inoculation over a period of weeks to months. After experimental HPV inoculation, it requires from 2 to 9 months for a verruca to become clinically apparent. This observation implies a relatively long period of subclinical infection. In our patient, the verruca appeared 4 months after grafting. It is unclear whether the verruca vulgaris resulted from direct contact with the operators hand during the surgical procedure, or with another person after grafting. However, there are several possible mechanisms of viral transmission from the operator to the patient: the operator may have palpated the lesion with his bare hand immediately after cryosurgery to evaluate the effectiveness of the freezing, or transmission may have occurred during application of a dressing after surgery. We suggest that the risk of transmission of infection from doctor to patient should be considered as a new complication of epidermal grafting.

Leg Ulcers and Pain: A Review

Leg ulcers are a common health problem. Ulcers of any etiology including venous ulcers may be very painful, but until recently, health professionals have not been good at recognizing or managing this type of pain. It is important to clarify the type, severity, and frequency of pain and to anticipate pain at dressing changes. The measurement of pain by the use of pain scales is very useful, particularly in assessing the efficacy of an intervention. Neuropathic pain and unusually painful ulcerations are discussed in this article.

Expression of sarco/endo-plasmic reticulum Ca2+-ATPase type 2 isoforms (SERCA2) in normal human skin and mucosa, and Darier's disease skin.

Summary Background The recent report that mutations in ATP2A2, which encodes the Ca2+ transporting sarco/endo‐plasmic reticulum pump type 2 isoforms (SERCA2), cause Dariers disease (DD) suggests that SERCA2 plays an important role in epidermal cell adhesion and differentiation. However, no data exist regarding SERCA2 expression in normal human skin, mucosa and DD.