Debilitating hip degeneration in trichothiodystrophy: Association with ERCC2/XPD mutations, osteosclerosis, osteopenia, coxa valga, contractures, and osteonecrosis.

Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder of DNA repair and transcription with developmental delay and abnormalities in brain, eye, skin, nervous, and musculoskeletal systems. We followed a cohort of 37 patients with TTD at the National Institutes of Health (NIH) from 2001 to 2019 with a median age at last observation of 12 years (range 2-36). Some children with TTD developed rapidly debilitating hip degeneration (DHD): a distinctive pattern of hip pain, inability to walk, and avascular necrosis on imaging. Ten (27%) of the 37 patients had DHD at median age 8 years (range 5-12), followed by onset of imaging findings at median age 9 years (range 5-13). All 10 had mutations in the ERCC2/XPD gene. In 7 of the 10 affected patients, DHD rapidly became bilateral. DHD was associated with coxa valga, central osteosclerosis with peripheral osteopenia of the skeleton, and contractures/tightness of the lower limbs. Except for one patient, surgical interventions were generally not effective at preventing DHD. Four patients with DHD died at a median age of 11 years (range 9-15). TTD patients with ERCC2/XPD gene mutations have a high risk of musculoskeletal abnormalities and DHD leading to poor outcomes. Monitoring by history, physical examination, imaging, and by physical medicine and rehabilitation specialists may be warranted.

The burden of cutaneous disease in solid organ transplant recipients of color.

Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin.

Kidney Stones are Prevalent in Individuals with Pseudoxanthoma Elasticum, a Genetic Ectopic Mineralization Disorder.

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder caused by loss-of-function mutations in the ABCC6 gene. While PXE is characterized by ectopic mineralization of connective tissues clinically affecting the skin, eyes, and cardiovascular system, kidney stones were reported in some individuals with PXE. The aim of this study is to determine whether kidney stones are an incidental finding or a frequent manifestation of PXE. We investigated the genetic basis of two siblings diagnosed with PXE. The younger patient presented with recurrent kidney stones since age 8. To address whether kidney stones are associated with PXE, the prevalence of kidney stones in a survey cohort of 563 respondents with PXE was compared to that of a general U.S. population survey, NHANES (National Health and Nutrition Examination Survey), with 28,629 participants. Genetic analysis in both patients identified compound heterozygous mutations in ABCC6, c.2787+1G>T and c.3774_3775insC. The analysis of participants aged 20 and older revealed that 23.4% of PXE patients had previously had a kidney stone, a significant increase compared to 9.2% in the general population. In addition, 17.8% of PXE patients reported their first kidney stone episode before age 18. PXE correlates with an increased risk of developing kidney stones with considerable morbidity and health-care cost.

Risk factors for keratinocyte carcinoma skin cancer in nonwhite individuals: A retrospective analysis.

BACKGROUND: Because most of the US population will consist of nonwhite individuals by the year 2043, it is essential that both physicians and patients are educated about skin cancer in nonwhite persons. OBJECTIVE: To update the epidemiology, investigate specific risk factors, and facilitate earlier diagnosis and intervention of keratinocyte carcinoma in nonwhite individuals. METHODS: Institutional review board-approved retrospective chart review of all nonwhite patients who had received a biopsy-proven diagnosis of skin cancer at Drexel Dermatology during June 2008-June 2015. RESULTS: Squamous cell carcinoma (SCC) was the most commonly diagnosed skin cancer in black and Asian populations, and basal cell carcinoma was the most common skin cancer in Hispanics. Black persons exhibited the majority of their SCC lesions in sun-protected areas, particularly the anogenital area. On average, current smokers received skin cancer diagnoses 12.27 years earlier than former smokers and 9.36 years earlier than nonsmokers. LIMITATIONS: Single-center design and interpractitioner variability of skin examination. CONCLUSION: The importance of lesions in photoprotected areas in nonwhite individuals should not go overlooked. However, emphasis should also be placed on active examination of sun-protected areas in nonwhite persons and recognition of the relationship between human papillomavirus and genital SCC lesions. Smoking cessation should be integrated in dermatologic counseling of all patients. Interventions tailored to each of these ethnic groups are needed.

Mohs micrographic surgery for digital melanoma and nonmelanoma skin cancers.

Treatment of digital skin cancers is challenging due to various functional and cosmetic implications. Traditionally, routine treatment includes radical amputation, but digital skin cancers are increasingly being treated with more conservative, tissue-sparing methods such as Mohs micrographic surgery (MMS), which provides excellent tissue conservation and margin control when used to treat melanoma and nonmelanoma skin cancers (NMSCs). In this study, we conducted a retrospective chart review to evaluate clinical outcomes following MMS for treatment of digital melanoma and NMSCs.

Psoriasis, chronic tonsillitis, and biofilms: Tonsillar pathologic findings supporting a microbial hypothesis.

Group A Streptococcus has been identified as a possible etiologic agent in psoriasis in epidemiologic, immunologic, immunopathologic, medical, and surgical studies. Tonsillectomy has been shown to provide considerable relief to 75% of patients with plaque psoriasis. Even with the substantial evidence supporting group A Streptococcus as a causative pathogen in psoriasis, it is an elusive pathogen because it is not culturable, nor does it exhibit any positive serologic evidence of its presence. One possible reason for the negative cultures and negative serology findings with group A Streptococcus is the development of biofilms. We conducted a pathologic study to determine whether biofilms were present in the tonsillar tissues of 10 patients with psoriasis-6 men and 4 women, aged 25 to 64 years (mean: 48)-and in 10 age- and sex-matched controls with chronic tonsillitis who did not have psoriasis. We found that biofilms were present in every tonsillectomy specimen we examined, including those of the controls. Whereas psoriasis has been considered a "double hit" phenomenon, we believe that the development of skin lesions is likely attributable to the presence of the gene PSORS together with the biofilm in psoriasis patients rather than to the biofilm itself. Biofilms have been identified in both extra- and intracellular locations. We believe our findings add further evidence supporting a microbial pathogenesis of this disease.

Isolation of Leclercia adecarboxylata from a patient with a subungual splinter.

Leclercia adecarboxylata is a rarely described motile, aerobic, gram-negative bacillus reported to cause clinically significant solitary infections in immunocompromised patients and polymicrobial wound infections in immunocompetent patients [1-5]. We present a case of a polymicrobial infection including L. adecarboxylata in a healthy female patient with a subungual splinter, to increase awareness and aid in the diagnosis and treatment of cutaneous L. adecarboxylata infections. To our knowledge, this is the first reported case of trauma-related subungual L. adecarboxylata infection reported in the dermatology literature.