Background Epidemiologic studies have associated tanning bed exposure and cutaneous melanoma. The relationship between the extent of tanning bed exposure and the risk of melanoma has not been elucidated in detail.Methods Surveys assessing the extent of tanning bed exposure and the history of skin cancer, including malignant melanoma, were collected from academic dermatology clinic patients ( n = 1518). Of these, 551 (36.3%) completed all components of the survey. The available medical records, including pathology reports ( n = 501; 33%), were reviewed to confirm cases of skin cancer. Data on potential confounding factors, including indoor vs. outdoor occupation and leisure activities, Fitzpatrick skin type, history of blistering sunburn, use of sunscreen and sun protective clothing, history of phototherapy, and level of education, were assessed and compared.Results Of the patients surveyed, 487 (32.1%) reported tanning bed exposure. Women aged 45 years or younger accounted for about 60% of all tanning bed users. Seventy-nine cases of malignant melanoma were reported, 22 in women aged 45 years or younger. In the entire cohort, the "ever-use" of tanning beds was found to be a significant risk factor for the development of melanoma [ P < 0.05; odds ratio (OR), 1.64; 95% confidence interval (95% CI), 1.01-2.67]. The risk was greater in women aged 45 years or younger ( P < 0.05; OR, 3.22; 95% CI, 1.01-11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min ( P < 0.01; OR, 3.18; 95% CI, 1.48 -6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI, 1.41-12.02). Limitations The study was subject to recall bias, included only patients at a midwestern academic practice, and had a relatively low response rate. ConclusionExposure to tanning beds increases the risk of malignant melanoma, especially in women aged 45 years or younger. These findings reinforce the hazards of tanning bed exposure.

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Differences in the perceptive importance and personal practice of sun protection are reflected in the self-reported clinical practice of these primary care physicians. This reinforces the opportunity to educate primary care clinicians to join the public health effort to increase sun protection awareness.

RATIONALE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare condition caused by mutations in FOXP3 resulting in defective regulatory T-cells (T regs ). We report two siblings with clinical presentations suggestive of IPEX with a novel variant in FOXP3. METHODS:A 5-year-old male (proband) was evaluated for diarrhea since infancy, intermittent fevers and arthralgias. Fecal calprotectin was markedly elevated and a colonic biopsy revealed findings of nonspecific inflammatory colitis, responsive to high-dose steroids. Family history was notable for type 1 diabetes mellitus in a 14 year-old brother who was subsequently diagnosed with nonspecific inflammatory colitis. Targeted gene sequencing (Invitae, Illumina) was performed in the siblings and parents. FOXP3 expression was evaluated by flow cytometry in CD3 + CD4 + CD25 + T reg cells. In the proband, LRBA expression was assessed in monocytes, T, B and NK cells. Tr1 (CD3 + CD4 + CD45A -CD49b + LAG-3 -) and Tr1/Th3 (CD3 + CD4 + CD25 -CD127 + ) precursor cells were also evaluated. RESULTS: Sequence analysis for both siblings revealed familial variants of uncertain significance (VUS) in FOXP3 [c.1129C>G(p.His377Asp0)]. The proband also had 2 VUS in LRBA [c.3905C>T(p.Thr1302lle) and c.7675G>T(p.Ala2559Ser)]. The same LRBA variants were inherited in cis from the proband's unaffected father and LRBA protein expression was normal in all cells types analyzed. Both siblings had normal or increased percentages CD3 + CD4 + CD25 + FOXP3 + T regs cells. Tr1 and Tr1/Th3 precursor were normal (proband). CONCLUSIONS: These are the first reported cases of IPEX syndrome resulting from this novel FOXP3 variant. FOXP3 expression may be normal in patients with IPEX syndrome. Hematopoietic stem cell transplantation is being considered pending T regs suppression assays.

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