Design  Prospective, longitudinal study. Laboratory tests and clinical evaluations were performed monthly for 6 months and then every 2 to 3 months (median follow-up, 13.4 months).

Setting  Tertiary care medical center.

Patients  Twenty-seven patients with immunobullous disease treated with azathioprine were enrolled during a 2-year period. Twelve met the criteria for evaluation of optimal levels of 6-thioguanine nucleotide.

Main Outcome Measures  Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment.

Results  The range of 6-thioguanine nucleotide was 48 to 457 pmol/8 x 10⁸ red blood cells (RBCs), with an average optimal level of 190.7 pmol/8 x 10⁸ RBCs for all patients. The mean optimal levels were 179.4 and 205.6 pmol/8 x 10⁸ RBCs for pemphigus and pemphigoid, respectively. Limited disease required less 6-thioguanine, with a mean of 145.3 pmol/8 x 10⁸ RBCs. Longitudinal induction of thiopurine methyltransferase activity was observed during treatment. Patients with recalcitrant disease showed higher induction of enzyme activity (with an increase of 9.1 to 23.6 U/mL of RBCs above baseline) than did those with responsive disease.

Conclusions  Optimal levels of 6-thioguanine nucleotide metabolites for disease remission in dermatology patients are 150 to 300 pmol/8 x 10⁸ RBCs. High levels of the inactive metabolite 6-methylmercaptopurine and induction of thiopurine methyltransferase are associated with recalcitrant disease.

Design  Case series.

Setting  Referral center: Department of Dermatology (La Rabta Hospital), Tunis, Tunisia.

Patients  Eight large Tunisian families with DD, with a total of 23 patients and 9 unaffected family members.

Main Outcome Measure  Patients were investigated at the clinical, histological, and genetic levels. Families were genotyped with 5 microsatellite markers spanning the ATP2A2 gene. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene.

Results  Typical clinical features of DD were constantly present. Phenotypic variation within and between the studied families was observed. Different neuropsychiatric disorders were seen in 5 families, and various cutaneous and extracutaneous original clinical associations were observed. The haplotype analysis led to the identification of different haplotypes cosegregating with the disease in the studied families. Mutation screening of the ATP2A2 gene revealed 3 recurrent mutations (119-120delAG, R677X, and D702N) and 4 novel variations: 2 missense mutations (G217A and L900R), one microinsertion (2772-2779 ins C), and one microdeletion (1747-1749 del 2T).

Conclusions  Our findings provide evidence for clinical and mutational heterogeneity of Tunisian families with DD. No obvious phenotype-genotype correlation was established. To our knowledge, this is the first molecular investigation of DD in the North African population.

Design  Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation.

Setting  Academic referral center.

Patients  Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage.

Interventions  Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment.

Main Outcome Measures  Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires.

Results  One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1β), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again.

Conclusions  Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.

Design  Retrospective cohort study.

Setting  The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics.

Patients  A total of 48 patients with pcALCL evaluated from 1990 through 2005.

Main Outcome Measures  Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays.

Results  Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters.

Conclusions  Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.

Observations  We describe the distinctive clinicopathologic features that were observed in 3 patients with an unusual variant of primary cutaneous T-cell lymphoma. All cases originated on the legs of elderly patients and exhibited a locally aggressive clinical behavior with relatively rapid relapses after radiotherapy and resistance to other therapies. Histologically, dense dermal-centered infiltrates of atypical, variably sized mature helper T cells were identified. One patient died of progressive disease.

Conclusions  Rare cases of primary cutaneous lymphomas do not necessarily fit current criteria for a standard diagnostic category but may represent unique clinicopathologic entities, such as primary cutaneous T-cell lymphoma localized to the lower leg. It is important to be able to identify these unusual lymphoma variants for prognosis and adequate treatment. The aggressive nature of lymphomas preferentially localized on the lower extremities may not be restricted to B-cell or cytotoxic neoplasms.

Observations  We describe an 84-year-old man who developed AGEP on 2 separate occasions after receiving an infusion of an ioversol-containing radiocontrast dye.

Conclusion  Acute generalized exanthematous pustulosis may occur after the use of intravenous radiocontrast dye.

Observations  A young woman was observed to have clinical lightening of her garment nevus and satellite nevi during 2 sequential pregnancies. Postpartum, the patient experienced darkening and repigmentation in her large garment nevus, with continued lightening of nearby satellite lesions. In addition to photographic documentation of these changes, biopsy samples taken during pregnant and nonpregnant periods underwent immunohistochemical evaluation for estrogen receptor β (ERβ), the predominant estrogen receptor in nevi and melanomas. Biopsy samples collected during pregnancy showed a decrease in nuclear staining for ERβ compared with samples collected after pregnancy. These changes in ERβ expression were not associated with histologic atypia during pregnancy or after delivery.

Conclusions  Congenital nevi may be unique in their response to altered estrogen levels. Given the slightly increased risk of melanoma in giant congenital nevi and the dearth of information available regarding the effects of pregnancy on congenital nevi, this case illustrates the need for further study of these pigmented lesions.

Observations  We assessed 2 Brazilian families with either lichen-type (family 1 had 14 affected subjects) or macular-type (family 2 had 7 affected subjects) PLCA. Typically, in both pedigrees, the onset of symptoms was around puberty, and pruritus usually began on the lower legs. Findings from lesional skin biopsy samples from both families showed thioflavin T–positive material in the papillary dermis, which was more prominent in the lichen phenotype in family 1. Spontaneous improvement occurred in 3 subjects (from both families) after age 25 years. All affected individuals in family 1 had a heterozygous missense mutation in the OSMR gene (p.I691T), but no pathogenic mutation in OSMR was found in family 2.

Conclusions  Familial PLCA shows autosomal dominant inheritance, but there is clinical and genetic heterogeneity and variable clinical penetrance. Demonstration of mutations in the OSMR gene provides new insight into mechanisms of itch and apoptosis in human skin.

Design  Observational study.

Setting  Large Department of Veterans Affairs hospital.

Patients  The study included 3236 patients with psoriasis and 2500 patients without psoriasis (controls).

Main Outcome Measures  Using International Classification of Diseases, Ninth Revision, Clinical Modification, codes, we compared the prevalence of traditional cardiovascular risk factors and other vascular diseases as well as mortality between patients with psoriasis and controls.

Results  Similar to previous studies, we found a higher prevalence of diabetes mellitus, hypertension, dyslipidemia, and smoking in patients with psoriasis. After controlling for these variables, we found a higher prevalence not only of ischemic heart disease (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.51-2.11) but also of cerebrovascular (OR, 1.70; 95% CI, 1.33-2.17) and peripheral vascular (OR, 1.98; 95% CI, 1.32-2.82) diseases in patients with psoriasis compared with controls. Psoriasis was also found to be an independent risk factor for mortality (OR, 1.86; 95% CI, 1.56-2.21).

Conclusions  Psoriasis is associated with atherosclerosis. This association applies to coronary artery, cerebrovascular, and peripheral vascular diseases and results in increased mortality.