Correspondence 1379 5 Chang MW, Miner JE, Moiin A, Hashimoto K. Iododerma after computed tomographic scan with intravenous radiopaque contrast media. J Am Acad Dermatol 1997; 36:1014–16. 6 Masse M, Falanga V, Zhou LH. Use of topical povidone-iodine resulting in an iododerma-like eruption. J Dermatol 2008; 35:744–7. 7 Vaillant L, Pengloan J, Blanchier D et al. Iododerma and acute respiratory distress with leucocytoclastic vasculitis following the intravenous injection of contrast medium. Clin Exp Dermatol 1990; 15:232–3. 8 Lauret P, Godin M, Bravard P. Vegetating iodides after an intravenous pyelogram. Dermatologica 1985; 171:463–8. 9 Khan F, Einbinder JM, Seriff NS. Suppurative ulcerating iododerma — a rare manifestation of inorganic iodide hypersensitivity. N Engl J Med 1973; 289:1018–20. 10 Miranda-Romero A, Sanchez-Sambucety P, Esquivias Gomez JI et al. Vegetating iododerma with fatal outcome. Dermatology 1999; 198:295–7. Funding sources: none. Conflicts of interest: none.

Vitamin D status in hidradenitis suppurativa DOI: 10.1111/bjd.12900 DEAR EDITOR, Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disorder of follicular occlusion characterized by double comedones, painful recurrent abscesses, sinus tract formation, scarring and architectural remodelling. It is associated with cigarette smoking and obesity. The sites most commonly affected are the axillae, inguinal and submammary folds, and the perineum.1 Vitamin D deficiency has been associated with a variety of nonskeletal diseases, including systemic lupus erythematosus (SLE), cardiovascular disease, rheumatoid arthritis (RA) and malignancies, but the evidence is deemed inconsistent and inconclusive.2 Vitamin D status is easily and accurately determined by measurement of 25hydroxyvitamin D (25OHD), and has not previously been assessed in HS. Sixteen patients (four men and 12 women) with HS were sequentially recruited after approval from the local ethics and medical research committee. The mean  SD age was 391  127 years, the mean disease duration was 149  70 years and the mean body mass index (BMI) was 321  72 kg m 2. Three patients had stage 3 Hurley disease, 12 had stage 2 Hurley disease and one had stage 1 Hurley disease. Ten patients were smokers. None of the patients was taking vitamin D supplements or had a history of skeletal fracture in the previous 3 years. Serum 25OHD was measured by electrochemiluminescence immunoassay, as previously described.3 C-reactive protein (CRP) was measured by immunoturbidimetry. Three patients had samples taken in winter, five in spring, four in summer © 2014 British Association of Dermatologists

and four in autumn. The median 25OHD level was 287 nmol L 1 (absolute range 102–833). Ten (63%) patients had serum 25OHD levels of < 30 nmol L 1, indicating a risk of deficiency.2 Two patients had a 25OHD level of < 50 nmol L 1; only four patients (25%) had a 25OHD level of > 50 nmol L 1. There was no correlation between 25OHD and BMI (r = 003, P = 091), CRP (r = 013, P = 066) or cigarette smoking (r = 003, P = 092). Poor vitamin D status is commonly reported in a number of conditions, and associations with psoriasis,4 SLE, RA,2 multiple sclerosis, several solid organ malignancies, cardiovascular disease, diabetes2 and malignant melanoma5 have been demonstrated. It has recently been suggested that low levels of 25OHD may be a result of inflammation.6 The direction of this association is not known, but it is suggested that reverse causation is likely.2,7,8 There is no convincing evidence that vitamin D supplementation has a beneficial effect on any of these conditions.8,9 To the best of our knowledge, this is the first study to assess vitamin D status in HS. HS is characterized by systemic inflammation, and an increased prevalence of obesity and smoking.1 It is possible that any or all of these factors, as well as reverse causation, could have contributed to the poor vitamin D status in our patients. Regardless of the cause, 75% of patients with HS in our small pilot study had a 25OHD level of < 50 nmol L 1 and would therefore benefit from dietary advice and vitamin D supplementation in order to optimize bone health and minimize the risk of fracture.2 It appears that vitamin D insufficiency is more profound in the HS population than in the general Irish population, in which the year-round prevalence rate has been reported to be 40% for a 25OHD level of < 50 nmol L 1.10 The issue of whether poor vitamin D status is a modifiable risk factor in HS needs investigation. 1

Dermatology Research Group, Education and Research Centre, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland 2 Dermatology Department, Adelaide and Meath Hospital Incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland 3 Metabolism Laboratory, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland E-mail: [email protected]

G. KELLY1 C.M. SWEENEY1 R. FITZGERALD2 M.P. O’KEANE3 M. KILBANE3 A. LALLY1 A.M. TOBIN2 M.J. MCKENNA3 B. KIRBY1

References 1 Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol 2009; 60:539–61. 2 Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press, 2011. 3 Walsh JM, McGowan CA, Kilbane M et al. The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth. Reprod Sci 2013; 20:536–41. British Journal of Dermatology (2014) 170, pp1373–1383

1380 Correspondence 4 Gisondi P, Rossini M, Di Cesare A et al. Vitamin D status in patients with chronic plaque psoriasis. Br J Dermatol 2012; 166:505–10. 5 Field S, Newton-Bishop JA. Melanoma and vitamin D. Mol Oncol 2011; 5:197–214. 6 Waldron JL, Ashby HL, Cornes MP et al. Vitamin D: a negative acute phase reactant. J Clin Pathol 2013; 66:620–2. 7 Shee C. Is hypovitaminosis D a consequence rather than cause of disease? Thorax 2013; 68:679. 8 Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2:76–89. 9 Bouillon R, Van Shoor NM, Gielen E et al. Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. J Clin Endocrinol Metab 2013; 98:E1283–304. 10 Cashman KD, Muldowney S, McNulty B et al. Vitamin D status of Irish adults: findings from the National Adult Nutrition Survey. Br J Nutrition 2013; 109:1248–56. Funding sources: none. Conflict of interests: none declared.

Individuals with complete filaggrin deficiency may have an increased risk of squamous cell carcinoma DOI: 10.1111/bjd.12911 DEAR EDITOR, Loss-of-function mutations in the filaggrin gene (FLG) are observed in approximately 10% of Northern Europeans. Heterozygous and homozygous mutation carriers have, respectively, partial or complete reduction of epidermal filaggrin and its degradation products. Filaggrin is degraded to, among other things, transurocanic acid (trans-UCA),1 a chromophore that provides protection against ultraviolet radiation (UVR) and modulates cutaneous immune functions.1 Accordingly, a deficiency of filaggrin leads to altered endogenous protection against UV exposure.1 Mutations in FLG are associated with atopic dermatitis (AD).2 Interestingly, individuals with AD appear to have an increased risk of developing nonmelanoma skin cancer, including squamous cell carcinoma (SCC).3 As SCC is strongly related to chronic ultraviolet (UV) exposure, we evaluated whether the prevalence of FLG mutations in patients diagnosed with SCC was higher than in controls from the general population. Briefly, 528 formalin-fixed, consecutive, archived, anonymized, paraffin-embedded blocks from patients diagnosed with SCC were retrieved from the Department of Pathology, Herlev Hospital, Copenhagen, Denmark. Approval was obtained from the local ethics committee (approval H-4-2011-145). The pretest sample size for identifying a 15-times higher prevalence of complete filaggrin-deficient individuals in the SCC group compared with the two control populations (80% power and P-value of 005) were calculation to 528 (Health06)4 and 197 (Inter99),5 respectively, or 286 for the British Journal of Dermatology (2014) 170, pp1373–1383

combined control groups. A pathologist confirmed the diagnosis of SCC on a haematoxylin and eosin-stained microscopic slide. Following this, a 3-mm punch biopsy of the cellular tumour area was obtained from the paraffin-embedded tissue. After overnight digestion with proteinase K, genomic DNA was extracted using silica-based magnetic particles (QIAsymphonyâ DNA Mini Kit on the QIAsymphony SP workstation; QIAGEN, Hilden, Germany), according to manufacturer’s instructions. The DNA concentration of the samples was measured using a NanoDropTM spectrophotometer (NanoDrop, Wilmington, DE, U.S.A.). Of the SCC samples, 492 (932%) were successfully genotyped by a suspension array-based, allele-specific polymerase chain reaction (Luminexâ; Luminex, Austin, TX, U.S.A.) previously described for the three most common loss-of-function mutations in the profilaggrin gene (GenBank NM_002016.1: c.1537C>T, c.2318_2321del, and c.7375C>T, commonly designated as R501X; 2282del4; and R2447X).6 Our data were compared with two unselected control populations obtained from the same area in Copenhagen, which had already been genotyped for the same three FLG mutations. A total of 6619 (976%) samples was successfully genotyped among samples from the Inter99 study, which included 6784 individuals (aged 30–60 years) from a general population.5 A total of 3346 (964%) samples was successfully genotyped from samples from the Health2006 study, which included 3471 Danish-born individuals aged 18–69 years.4 A chi-squared test was used to compare the prevalence of FLG mutations in the general population with patients with SCC. As both groups have a complete absence of filaggrin in the skin, we combined patients who were either compound heterozygous or homozygous for the FLG mutations.7 Loss-offunction mutations in the FLG were observed in 48 (98%) of 492 patients with SCC, six (12%) of whom were compound heterozygous or homozygous, and in 556 (84%) of 6619 and 297 (89%) of 3346 in controls, of whom seven (01%) and 11 (03%) were compound heterozygous or homozygous, respectively (Table 1). Individuals with heterozygous FLG mutations did not have an increased risk of SCC compared with controls [P = 031 (Inter99); P = 050 (Health06)]. Individuals who were either compound heterozygous or homozygous for the FLG mutations had a statistically increased risk of SCC compared with controls [P = 00001 (Inter99); P = 0015 (Health06)]. Individuals who were either compound heterozygous or homozygous for FLG mutations had a statistically significant increased risk of having SCC compared with controls [P = 0015, power 069 (Health06); P = 00001, power 093 (Inter99); combined power 088]. It seems plausible that individuals who were compound heterozygous or homozygous for the FLG mutations had an increased risk of SCC as they are less protected against chronic UV exposure. The pathomechanism is likely explained by a reduction in the amount of trans-UCA in the stratum corneum, leading to greater UV penetration into nucleated cell layers, with an increased risk of malignant transformation, as © 2014 British Association of Dermatologists

Vitamin D status in hidradenitis suppurativa.

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