T. Kanekura

Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus

Summary The rash of systemic lupus erythematosus (SLE) is usually treated with topical corticosteroids, but prolonged use causes adverse cutaneous side‐effects. We assessed the efficacy of topical tacrolimus for treating the skin lesions of SLE. Three patients with SLE affecting their facial skin applied 0·1% tacrolimus ointment on one side of their face twice daily for 3 weeks, in conjunction with a sunscreen cream. After 3 weeks, erythema on the treated side was ameliorated in all three patients compared with the untreated side. Although the study is preliminary, the results demonstrate that topical tacrolimus may be useful for treating the malar rash of SLE.

DNA hypermethylation of the forkhead box protein 3 (FOXP3) promoter in CD4+ T cells of patients with systemic sclerosis

Systemic sclerosis (SSc) is a complex autoimmune disease that involves dysregulation of immune homeostasis. The failure of impaired regulatory T cells (Tregs) to maintain immune homeostasis plays a major role in the development of SSc. Transcriptional silencing of the forkhead box protein 3 gene (FOXP3) via hypermethylation of regulatory regions has been identified as a hallmark of committed Tregs and several autoimmune disorders.

9-Cis-retinoic acid exhibits antifibrotic activity via the induction of cyclooxygenase-2 expression and prostaglandin E2 production in scleroderma fibroblasts.

Background.  The pathogenesis of scleroderma (SSc) is not fully understood, and there is no effective treatment for this chronic disease. Retinoic acid (RA) can modulate connective tissue metabolism, exhibit antifibrotic activity and improve the clinical symptoms of patients with SSc. However, the mechanisms by which RA elicits its antifibrotic actions remain to be determined.

Diagnostic usefulness of a nested polymerase chain reaction assay for detecting Sarcoptes scabiei DNA in skin scrapings from clinically suspected scabies.

1 Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161:987–1019. 2 Tyring S, Gordon KB, Poulin Y et al. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Arch Dermatol 2007; 143:719–26. 3 Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005. Br J Dermatol 2005; 153:486–97. 4 The electronic Medicines Compendium (eMC). Humira Pen and Syringe: Summary of Product Characteristics. 2009. Available at: http://emc. medicines.org.uk/document.aspx?documentId=21201 (last accessed 11 June 2010). 5 Gordon KB, Langley RG, Leonardi C et al. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol 2006; 55:598–606. 6 Menter A, Tyring SK, Gordon K et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58:106–15. 7 Saurat JH, Stingl G, Dubertret L et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008; 158:558–66. 8 Papoutsaki M, Chimenti MS, Costanzo A et al. Adalimumab for severe psoriasis and psoriatic arthritis: an open-label study in 30 patients previously treated with other biologics. J Am Acad Dermatol 2007; 57:269–75. 9 Martyn-Simmons CL, Green L, Ash G et al. Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation. J Eur Acad Dermatol Venereol 2009; 23:1394–7. 10 Lecluse LL, de Groot M, Bos JD, Spuls PI. Experience with biologics for psoriasis in daily practice: switching is worth a try. Br J Dermatol 2009; 161:948–51. 11 Ryan C, Kirby B, Collins P, Rogers S. Adalimumab treatment for severe recalcitrant chronic plaque psoriasis. Clin Exp Dermatol 2009; 34:784–8. 12 Bartelds GM, Wijbrandts CA, Nurmohamed MT et al. Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study. Ann Rheum Dis 2010; 69:817–21.

A case of malignant atrophic papulosis successfully treated with nicotine patches

SIR, We report diffuse and reversible hair loss in three patients treated with octreotide. We propose that patients treated with octreotide should be informed that hair loss is a possible but reversible side-effect. The alopecia occurred in patients treated with octreotide after surgical excision of a somatotropic macroadenoma, without any previous radiotherapy. Review of the literature revealed eight other cases of diffuse hair loss associated with octreotide treatment. It is likely that this sideeffect is under-reported in the literature. It is difficult to explain this scalp hair loss by a hormonal deficiency. Octreotide is an analogue of somatostatin used in treatment of acromegaly, after surgery or radiotherapy failure or when surgery is not possible. It is also used for symptomatic treatment of some digestive endocrine tumours such as glucagonoma, carcinoid tumours and corticotropic (Nelson syndrome) primitive thyreotropic adenomas, and to prevent pancreatic fistula after surgery. Two somatostatin analogues are available: octreotide (Sandostatin , Novartis) and lanreotide (Somatuline , Ipsen). The somatostatin inhibits secretion of growth hormone (GH) and thyroid-stimulating hormone. Octreotide has a longer and stronger effect, reducing the number of injections required. Its usual side-effects are: pain at the injection site, impaired glucose tolerance, diarrhoea, steatorrhoea, gastrointestinal disturbances, abdominal cramps and gallstones. We describe three patients with scalp hair loss related to octreotide intake. Patient 1. A 36-year-old man consulted in October 2000 with diabetes and a dysmorphic acromegaly syndrome. He had no relevant medical history and was on no medication. His father had early androgenetic hair loss, but his eight brothers had not. A somatotropic macroadenoma with an extension in the left cavernous sinus was diagnosed. He underwent surgery in November 2000. In spite of the excision, somatotropic hypersecretion persisted (somatomedin C 600 ng mL; normal < 400) and octreotide was introduced in April 2001. He became euthyroid, with a low testosterone level (7Æ6 mmol L; normal 12–40) and a corticotropic insufficiency with an elevated urinary-free cortisol treated with hydrocortisone 20 mg daily. One month later, the patient started to lose his hair. He developed diffuse alopecia that increased during administration of oncemonthly injections of octreotide. After the sixth injection, octreotide was replaced with lanreotide. The hair loss completely reversed after the octreotide was withdrawn, without any dermatological treatment. Patient 2. A 42-year-old woman was treated for a somatotropic macroadenoma with octreotide for 3 months (May– August 2001) before trans-sphenoidal surgery in September 2001. Her medical history included hypothyroidism after hemithyroidectomy, dyslipidaemia and a gastric ulcer. Her usual medication consisted of levothyroxine, simvastatin, 19-norprogesterone and estradiol. After surgery, somatomedin C was high (500 ng mL), GH basal level was higher than normal, and GH secretion after an oral glucose tolerance test was still pathological; she had no pituitary insufficiency. She developed diffuse alopecia in the week following the third once-monthly injection of octreotide. Her body hair was unchanged. After octreotide treatment was interrupted, she had a partial recovery of scalp hair, with a positive traction test on tinted hair only, suggesting a natural repair process. Patient 3. A 67-year-old woman had an inoperable voluminous somatotropic macroadenoma. Her medical history included noninsulin-dependent diabetes and dyslipidaemia, and a total hysterectomy 26 years previously. Once-monthly injections of octreotide were commenced. After 3 months, she noticed a scalp hair loss that could not be attributed to other drugs or deficiencies. The alopecia was moderate and stopped quickly after octreotide interruption. Body hair was unchanged. Hair loss may present as a side-effect of octreotide. It is acute and diffuse, and presents as a telogen or anagen effluvium leading to reversible and nonscarring alopecia. Metabolic or hormonal alopecia was excluded as our patients had normal ferritin, blood counts, testosterone and cortisols, and were euthyroid. The pattern and spontaneous reversal were not consistent with androgenetic alopecia. The diagnosis of postmenopausal frontal fibrosing alopecia was excluded as the alopecia was diffuse and was not located in the frontal area. Examination revealed a nonscarring alopecia. The traction test was still positive but only on old hairs. Formal investigations such as a trichogram, daily hair count or hair wash test were not performed in our three patients. The pull test was positive only for patient 2 and only on her tinted hair; the hair which was not tinted was younger and the pull test was negative. It would have been interesting to perform a trichogram (proportion of anagen hairs to telogen hairs) to show a telogen hair predominance to confirm telogen effluvium, but the chronological and drug history are suggestive of this. Eight cases of diffuse hair loss associated with octreotide treatment were found in the literature: five women aged 41–64 years with acromegaly, a 56-year-old man with Crohn’s disease, a 40-year-old woman with familial polyposis and bowel infarction treated with octreotide as an adjunct to home parenteral nutrition in the management of a permanent endojejunostomy syndrome, and one patient with a severe dumping syndrome.

Immunoelectron-microscopic detection of globotriaosylceramide accumulated in the skin of patients with Fabry disease.

Background  Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of α‐galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL‐3). To date, no direct detection of GL‐3 by immunoelectron microscopy has been reported.

Improvement of adult Still's disease with granulocyte and monocyte adsorption apheresis.

Adult Stills disease is characterized by a high spiking fever, transient skin rash, and polyarthralgia. Joint pain is one of the major complaints and is often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy for treating arthralgia in adult Stills disease. A 33‐year‐old woman with adult Stills disease who suffered from recalcitrant arthralgia resistant to systemic corticosteroids was treated with GCAP therapy. She underwent five GCAP treatments at 5‐day intervals. Her joint pain responded dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating adult Stills disease. We present a detailed description of the patient and this novel therapy.

Classical juvenile pityriasis rubra pilaris in a patient with Down syndrome

We report a case of classical juvenile pityriasis rubra pilaris (CJPRP) in a 15‐year‐old boy with Down syndrome. The rash was extensive, severe, accompanied by intense itching and responded to low‐dose etretinate. Xerosis and cheilitis were also present, suggesting that keratinization defects associated with Down syndrome may be involved in the pathogenesis of CJPRP. PRP is a rare dermatological disorder and to the best of our knowledge, this is the first reported case of CJPRP in a patient with Down syndrome.

Morphological, biochemical and molecular biological characteristics of a granulocyte colony-stimulating factor-producing human eccrine carcinoma cell line.

We describe here a newly established cell line from an eccrine carcinoma which produced an abundant amount of granulocyte colony-stimulating factor (G-CSF). An eccrine carcinoma of the scalp of a 69 year-old-Japanese female had metastasized to the pleura. Clinically, she had marked neutrophilia (up to 60,000/mm3), and a high level of G-CSF (38.7 x 10(3) pg/ml) was detected in the pleural effusion, as determined by enzyme-linked immunosorbent assay (ELISA). We established a cell line in vitro and maintained the cells in culture for 30 months in 90 subcultures. We investigated whether these tumor cells were able to produce G-CSF in culture and found that they were. We also found that the amount of G-CSF produced paralleled the rise in cell number (26.5 x 10(3) pg/ml at confluency). When culture media were administered to rabbits (25 ml/rabbit), the amount of circulating neutrophils increased until the number was equal to or greater than that resulting from injection of recombinant human G-CSF (rhG-CSF)(75 micrograms). This effect persisted for 7 days. When tumors were induced in SCID and nude mice by injecting cultured cells (1 x 10(7) cells/mouse), the number of circulating neutrophils also correlated well with tumor size in these mice (200,000/mm3, 3 cm tumor). After tumor removal, the neutrophil number returned to normal within 30 days. G-CSFmRNA in cultured, cells was detected by RT-PCR. Based on these results, it was confirmed that the marked neutrophilia observed in the patient was caused by the tumor-generated G-CSF. This is the first G-CSF-producing cell line developed from a cancer of the skin.

EPIDERMAL NEVUS SYNDROME WITH HEMANGIOMA SIMPLEX

To the editor: We observed a case of epidermal nevus syndrome (ENS) associated with hemangioma simplex. A survey of the literaturte of the last 20 years revealed 161 (1,2) cases of ENS; only 4 (3, 4) were associated with hemangioma simplex. We present here a detailed description of our case and provide a brief discussion of the distinction between this association and phacomatosis pigmentovascularis type I. Case report: A l-year-old boy was referred to our clinic with skin lesions on the abdomen, right lower leg, and face which had been present since birth. Clinical examination revealed grayish brown papules with a hyperkeratotic papillomatous surface which had aggregated to form linear lesions. The