Vitamin D3 and deconvoluting a rash.

BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash.METHODSSkin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks.RESULTSCholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement.CONCLUSIONHigh-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses.TRIAL REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).

Incidence of missing pathology specimens in dermatology.

BACKGROUND: Occasionally specimen containers are received in the dermatopathology laboratory without an accompanying specimen. The consequences in this scenario can range from delay in care and inconvenience to patients to increased morbidity and even mortality. Data regarding incidence and associated characteristics of missing specimens are scant. METHODS: Over a 10-year period (7 January 2010 to 7 January 2020) all cases with a missing specimen in a single academic dermatopathology laboratory and a single dermatopathology practice embedded within a dermatology practice were reviewed. RESULTS: Out of 270,754 specimens received, 83 empty specimen containers were identified for an incidence of 0.031%. There were 14 (0.005%) cases in which patients had a separate procedure and a second container with both specimens in it accompanying the empty container. The most common missing specimen-generating procedures were shave biopsies (51%) with most common clinical diagnosis being unspecified (30%). The most common specimen location from the 97 total specimen bottles containing either zero or two specimens was head/neck (53%). Although no further procedures were performed after the specimen was lost for 48% of cases, re-biopsy occurred for 28%. CONCLUSIONS: Failure to insert specimens into the correct container is rare, but represents a potential significant negative event where vigilance and improvement is required.

Spitz nevi in African Americans: A retrospective chart review of 11 patients.

BACKGROUND: Spitz nevi are benign melanocytic neoplasms that typically present as rapidly growing solitary lesions on the head, neck, or lower extremities. Very rare reports have been described in African Americans. METHODS: A single-institution 29-year retrospective review of African American patients diagnosed with Spitz nevi was thoroughly analyzed in order to characterize these rare clinical and histopathologic presentations. RESULTS: Eleven African Americans with spitzoid lesions were identified. Seven (64%) cases were in pediatric patients and nine (82%) were in females. Most lesions were hyperpigmented (73%) and elevated (82%). Six (55%) were compound Spitz nevi, three (27%) were dermal Spitz nevi, and two (18%) were junctional Spitz nevi. Two lesions had more than one atypical feature. Histopathologically, common features were symmetry, sharp circumscription, pagetoid spread (55%) with most being centrally, predominance of epithelioid cells (64%), Kamino bodies (45%), slight pigmentation (46%), maturation of dermal component with depth, and lack of subcutaneous fat involvement or ulceration. Excision was performed on all patients and there were no recurrences although follow-up was limited. CONCLUSION: Awareness of the possibility and various presentations of Spitz nevi in African Americans will help prevent misdiagnosis.

Hormone receptor expression in patients with dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma for which the exact etiology is unknown. Case reports exist of DFSP appearing and growing rapidly during pregnancy, suggesting a hormonal role. OBJECTIVE: Our goal was to determine the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in patients with DFSP. METHODS: Archived formalin-fixed, paraffin-embedded tissue from patients with DFSP in the past 20 years at a single institution were analyzed for ER and PR using immunohistochemistry. A semiquantitative scoring method was used to evaluate the expression as positive or negative. Analysis was used to determine whether there was an association between receptor positivity and tumor site, age at diagnosis, sex, race, or disease recurrence. RESULTS: Forty-four patients with DFSP were included in the study. Tumors were 22.7% ER+/PR+, 34.1% ER+/PR-, 9.1% ER-/PR+, and 34.1% ER-/PR-. There was no significant association between expression of ER and PR and sex, age at diagnosis, race, or tumor location. Loss of receptor expression was observed in all recurrent tumors. LIMITATIONS: This study is limited by a lack of follow-up and a new scoring system. CONCLUSIONS: The data presented warrant additional study to determine hormone receptor function and the potential efficacy of antihormone therapies for the treatment of patients with DFSP.

Systemic Evaluation of Electrical Stimulation for Ischemic Wound Therapy in a Preclinical In Vivo Model.

Objective: In a systematic preclinical investigation of ischemic wound healing, we investigated the hypothesis that electrical stimulation (ES) promotes the healing of ischemic wounds. Approach: The effects of varying clinically relevant ES variables were evaluated using our modified version of the Gould F344 rat ischemic wound model. Stimulation was delivered using the novel lightweight integrated, single-channel, current-controlled modular surface stimulation (MSS) device. Stepwise variation allowed the effects of five different stimulation paradigms within an appropriate current density range to be studied. Within each group, 8-10 animals were treated for 28 days or until the ischemic wounds were healed and 5 animals were treated for 12 days. Eight rats received sham devices. A quantitative multivariable outcomes assessment procedure was used to evaluate the effects of ES. Results: Ischemic wounds treated with a decreased interpulse interval (IPI) had the highest rate of complete wound closure at 3 weeks. Wounds treated with decreased pulse amplitude (PA) had a lower proportion of closed wounds than sham ischemic wounds and showed sustained inflammation with a lack of wound contraction. Innovation: Our systematic study of varying ES paradigms using the novel MSS device provides preliminary insight into potential mechanisms of ES in ischemic wound healing. Conclusion: Clinically appropriate ES can more than double the proportion of ischemic wounds closed by 3 weeks in this model. Ninety percent of wounds treated with a decreased IPI healed by 21 days compared with only 29% of ischemic wounds treated with decreased PA, which appears to inhibit healing.

Histologic lichenoid features in oral dysplasia and squamous cell carcinoma.

OBJECTIVE: This study describes the occurrence of histopathologic characteristics of oral lichenoid mucositis in epithelial dysplasia and squamous cell carcinoma. STUDY DESIGN: This retrospective review examined 352 histologic specimens of group 1 (mild to moderate dysplasia), group 2 (severe dysplasia or carcinoma in situ), and group 3 (squamous cell carcinoma) for correlation between 5 histologic characteristics frequently found in oral lichen planus and grade, age, gender, and oral subsite. RESULTS: In this sample, 29% of all cases exhibited 3 or more lichenoid features. Lichenoid features were significantly more frequent in group 1 over group 2 lesions for cases meeting a minimum lichenoid threshold (P = .001). No statistically significant patterns were noted for age or gender. The buccal mucosa was significantly overrepresented (P = .039) and the floor of the mouth was significantly underrepresented (P = .049) in regard to lichenoid feature frequency. CONCLUSIONS: This study confirms the frequent correlation of lichenoid characteristics in oral premalignant and malignant lesions.

Cutaneous complications in hematopoietic cell transplant recipients: impact of biopsy on patient management.

The utility of cutaneous biopsies in directing the management of post-hematopoietic cell transplantation (HCT) eruptions remains uncertain. We retrospectively analyzed 439 consecutive HCT procedures for malignant hematologic disorders performed at our institution between January 2005 and December 2012; 192 patients underwent 430 cutaneous biopsies. The clinical and dermatopathologic diagnosis differed in 240 cases (56%). Biopsy results led to a change in therapy in 69 (16%) episodes. Seventeen of 69 management changes occurred in response to a clinical diagnosis of graft-versus-host disease and resulted in augmentation of systemic immunosuppression. The management was modified with similar frequencies with respect to concordance or discordance between the clinical and histopathologic diagnosis (P = .51). We used classification and regression tree (CART) analysis, a decision-modeling technique, to predict the biopsy yield as expressed by impact on clinical management in the allogeneic and autologous setting. The models were cross-validated and then tested against a validation subset, and they maintained a high negative predictive value and high specificity. Although skin biopsies may not be mandatory for either diagnostic or therapeutic reasons, in carefully chosen circumstances, this procedure can yield extremely important data. We believe a prospective study should be undertaken to evaluate current practice data and to validate our decision tree models.

Growth on demand: reviewing the mechanobiology of stretched skin.

Skin is a highly dynamic, autoregulated, living system that responds to mechanical stretch through a net gain in skin surface area. Tissue expansion uses the concept of controlled overstretch to grow extra skin for defect repair in situ. While the short-term mechanics of stretched skin have been studied intensely by testing explanted tissue samples ex vivo, we know very little about the long-term biomechanics and mechanobiology of living skin in vivo. Here we explore the long-term effects of mechanical stretch on the characteristics of living skin using a mathematical model for skin growth. We review the molecular mechanisms by which skin responds to mechanical loading and model their effects collectively in a single scalar-valued internal variable, the surface area growth. This allows us to adopt a continuum model for growing skin based on the multiplicative decomposition of the deformation gradient into a reversible elastic and an irreversible growth part. To demonstrate the inherent modularity of this approach, we implement growth as a user-defined constitutive subroutine into the general purpose implicit finite element program Abaqus/Standard. To illustrate the features of the model, we simulate the controlled area growth of skin in response to tissue expansion with multiple filling points in time. Our results demonstrate that the field theories of continuum mechanics can reliably predict the manipulation of thin biological membranes through mechanical overstretch. Our model could serve as a valuable tool to rationalize clinical process parameters such as expander geometry, expander size, filling volume, filling pressure, and inflation timing to minimize tissue necrosis and maximize patient comfort in plastic and reconstructive surgery. While initially developed for growing skin, our model can easily be generalized to arbitrary biological structures to explore the physiology and pathology of stretch-induced growth of other living systems such as hearts, arteries, bladders, intestines, ureters, muscles, and nerves.

A case of recurrent pseudolymphomatous folliculitis: A mimic of cutaneous lymphoma.

Pseudolymphomatous folliculitis is a rare entity. We present a 62-year-old man with a recurrent solitary nodule on his nose requiring multiple excisions. Microscopic examination of the excisions showed a dense lymphocytic infiltrate containing numerous histiocytes and S100+, CD1a+ dendritic cells that surrounded and infiltrated hypertrophic hair follicles. Diffuse sheets of CD3+ T cells and nodular clusters of CD20+ B cells were also seen. There was normal reactive pattern of follicular centers. Light chain restriction was not detected. T-cell receptor and immunoglobulin heavy chain gene rearrangements by polymerase chain reaction revealed negative findings. A diagnosis of pseudolymphomatous folliculitis was made based on the hypertrophic hair follicles, periadnexal S100+ and CD1a+ dendritic cells, and negative clonal gene rearrangement study findings. This case of recurrent pseudolymphomatous folliculitis is instructive because of the resemblance to cutaneous lymphomas and cutaneous lymphoid hyperplasias, and the need for correct diagnosis to avoid overtreatment of this indolent condition.

HIV and skin cancer.

AIDS produces profound alterations in normal immunity. Impaired cellular immunity permits new tumor formation as evidenced by the solid-organ transplant literature. The weakened cellular immune system of HIV-infected patients resembles in some ways the iatrogenic immunosuppression in solid-organ transplant recipients. This article summarizes what is known about skin cancer in the solid-organ transplant population and compares the immunodysregulation of HIV infection with the iatrogenic immunosuppression following solid-organ transplantation.