Dermatology consultation service at a large metropolitan hospital system serving minority populations.

BACKGROUND: Dermatology consultations in the inpatient hospital setting can improve diagnostic accuracy and management. OBJECTIVE: Characterize dermatologic diagnostic and treatment trends in the hospital setting and identify variables that may affect patient care. METHODS: Retrospective chart review from 1 January 2012 to 31 December 2017 at Jackson Memorial Hospital (JMH) (Miami, Florida, USA), an academic non-profit tertiary care centre affiliated with University of Miami Miller School of Medicine, was performed. Patients who received dermatology consultations in the emergency department (ED) or inpatient settings were included. Patient demographics, admission information, provisional diagnosis and management plans by primary teams, final diagnosis, management plans and testing recommendations by the dermatology consults team, and follow-up information were collected. Analysis using Microsoft Excel of how time to consultation, admission length, inpatient versus ED setting and primary team affected diagnostic accuracy was also performed. RESULTS: The 1004 consultations for 812 patients (n = 812) were reviewed (359 women, 453 men). Most patients were Hispanic (n = 359; 44.2%) or African American (n = 273; 33.6%). Mean admission length was 20.6 days (range 0-439; median 6). The most common consulting service was internal medicine (n = 452). In 387 cases (47.6%), primary teams did not give a provisional diagnosis. The most common provisional diagnoses were bacterial infection (n = 93), viral infection (n = 49) and drug reaction (n = 44). The most common diagnoses by dermatology were viral infection (n = 93), bacterial infection (n = 90) and drug reaction (n = 80). Dermatology consultation changed the provisional diagnosis in 55.7% of cases, more often in cases where consultation took place ≥2 days after admission (P < 0.05). Primary teams followed dermatology treatment recommendations in 85.2% of cases. CONCLUSION: Dermatology consultation improves diagnostic accuracy in skin disorders in the hospital setting and serves as a valuable resource for inpatient care. A notable aspect of data from this study is the unique patient population, predominantly comprised of underrepresented racial and ethnic minorities including Hispanics and African Americans.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase.

BACKGROUND: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I-II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. METHODS: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. RESULTS: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS-), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS- patients receiving at least four doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. CONCLUSION: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.

A novel rat model for chemotherapy-induced alopecia.

BACKGROUND: More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. AIM: To develop a clinically relevant adult rat model for CIA. METHODS: We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days. RESULTS: Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. CONCLUSIONS: A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA.

tert-butyl hydroperoxide, an organic peroxide, causes temporary delay in hair growth in a neonatal rat model.

tert-butyl hydroperoxide (tBHP), an organic peroxide, has been shown to cause irreversible damage to keratinocytes in vitro with prolonged administration at high concentrations, and reversible damage with short-term administration at low concentrations. To investigate the effects of tBHP on keratinocytes in vivo, we analysed hair growth in tBHP-treated neonatal rats. Sprague-Dawley and Long-Evans rat pups were injected subcutaneously with tBHP or vehicle once daily for 6 days, and hair growth was monitored. The tBHP-treated rats had a significant delay in hair growth. However, this delay reversed within days, and the hair coats, including hair pigmentation, of tBHP-treated and sham-treated rats were indistinguishable 2 weeks later. Histological analysis and BrdU labelling of S phase cells confirmed the delay in hair-follicle growth and its reversal in tBHP-treated rats. Our results indicated that the changes incurred in hair follicles by short-term use of high-dose oxidants in vivo are temporary and reversible.

Immunohistochemical evaluation of toxic epidermal necrolysis treated with human intravenous immunoglobulin.

AIM: Toxic epidermal necrolysis (TEN) is a severe drug reaction characterized by massive epidermal cell death. The authors of the current study and others have noted improved outcomes in TEN patients treated with human intravenous immunoglobulin (IVIG), purportedly due to its ability to inhibit the fas/fas-ligand (Fas-L) apoptotic pathway, but published case series evaluating TEN through the use of immunohistochemical antibody stains for Fas and Fas-L before and after IVIG treatment are lacking. The authors hypothesized that due to IVIG's ability to arrest the evolution of TEN, expression of Fas/Fas-L on keratinocytes would be decreased or absent following IVIG treatment. METHODS: Ten patients diagnosed with TEN underwent biopsies of their lesions prior to and five days after treatment with IVIG. Seven post-treatment biopsies were of sufficient quality to undergo evaluation. RESULTS: All ten pretreatment biopsies had Fas and Fas-L expression by immunohistochemistry, while six out of seven (85.7%) post-treatment biopsies failed to demonstrate Fas or Fas-L expression. One of seven post-treatment biopsies stained positive for Fas and Fas-L. CONCLUSION: This reduced immunohistochemical expression of apoptotic markers may represent IVIG inhibition of the pathogenic mechanism of TEN. Alternatively reduced Fas and Fas-L may be a feature of reepithelialization in TEN, or characteristic of rapidly proliferating epidermis.

Successful treatment of extramammary Paget's disease of the scrotum with imiquimod 5% cream.

Extramammary Paget's disease (EMPD) of the skin is an uncommon malignancy involving the epidermis, which sometimes extends into the dermis. Current treatments for EMPD are surgical excision, Mohs' micrographic surgery or laser ablation. We report a case of a 68-year-old male who presented with recurrent EMPD. The patient refused to have surgery and, as an alternative, he applied imiquimod 5% cream, an immune response modifier, daily for a total of 6 weeks. During the initial weeks of therapy, he experienced moderate erythema. Imiquimod treatment resulted in clinical and histological eradication of EMPD, with no recurrence observed during 6 months of follow-up.

Mucocutaneous pigmented macule as a result of zinc deposition.

BACKGROUND: Mucocutaneous depositions of various metals such as silver, lead, gold, arsenic, mercury, iron, and bismuth have been previously published. Heavy metal deposition typically occurs in the setting of either prolonged topical application to intact skin, topical application to eroded or ulcerated skin, as a result of either parenteral administration, or due to penetrating traumatic exposure. METHOD: We report a unique case of mucocutaneous pigmentation occurring in a snow skier after topical application of a zinc-containing sunblock. Formalin-fixed paraffin-embedded tissue was utilized for electron microscopy. RESULT: Backscatter electron imaging and energy dispersive spectroscopy revealed that the dominant metal present was zinc. CONCLUSIONS: Mucocutaneous deposition of metals is enhanced by damage to the surface epithelium. Metal-containing topical agents, although commonly used, may rarely result in a permanent pigmentary alteration. We believe similar cases of mucocutaneous deposition of zinc exist; however, as these may be currently misdiagnosed as amalgam tattoos, the true incidence of this disorder is presently undefined.

Seborrheic keratoses, solar lentigines, and lichenoid keratoses. Dermatoscopic features and correlation to histology and clinical signs.

Evaluation of the three benign lesions discussed here form the basis for dermoscopic evaluation of other pigmented skin lesions. The features of seborrheic keratosis, including [figure: see text] the various forms of fissures, comedo-like openings, and milia-like cysts, often allow easy interpretation of seborrheic keratosis; however, similar structures are commonly associated with melanocytic neoplasms, notably congenital nevi. Understanding solar lentigo and its dermoscopy features allows for the appreciation of pigment networks common in lentiginous melanocytic nevi and melanoma. The lichenoid keratosis is the model for lichenoid inflammation elsewhere, notably in halo nevi, regressing melanoma, and other melanocytic neoplasms with significant host inflammatory reactions.

Is there a special relationship between CD30-positive lymphoproliferative disorders and epidermal proliferation?

The relationship between CD30+ lymphoma and epithelial proliferations is not well defined. CD30+ lymphoma and lymphomatoid papulos (LyP) share immunohistochemical epitopes and some other features. A single case of LyP associated with multiple keratoacanthomas (KAs) was recently reported. We report two cases of atypical lymphocytic proliferation with features of CD30+ lymphoma and LyP intimately associated to KA and squamous cell carcinoma (SCC), KA type. This similar combination of an epidermal tumor and apparent involvement with atypical lymphocytic infiltrates raises the possibility of an association between the two entities. We speculate that the association may be more than expected to occur by chance and suggest several mechanisms by which the association may evolve.

Hematoxylin and safranin O staining of frozen sections.

Currently the hematoxylin and eosin staining procedure is the most popular among Mohs surgeons for histology. However, safranin O, a cheaper and relatively safer stain which is predominantly used for plant histology, should be considered as it offers similar or improved accuracy in the diagnosis of frozen sections of basal and squamous cell carcinomas.

Analysis of thyroid transcription factor-1 and cytokeratin 20 separates merkel cell carcinoma from small cell carcinoma of lung.

Merkel cell carcinoma needs to be separated from small cell carcinoma metastatic from visceral sites to skin. Pulmonary small cell carcinoma is the most common primary site of small cell carcinoma. We evaluated the immunophenotypic characteristics of 21 Merkel cell carcinomas and 33 small cell carcinomas of lung using thyroid transcription factor-1 and cytokeratin 20. Thyroid transcription factor-1 was 100% specific for the diagnosis of small cell carcinoma of lung associated with a diagnostic sensitivity of 85%. Cytokeratin 20 was present in 95% of Merkel cell carcinomas; however, 33% of small cell carcinoma of lung were also positive. Both antibodies typically demonstrate diffuse and intense staining of their respective tumor cells. We conclude that thyroid transcription factor-1 is a sensitive and specific marker for small cell carcinomas of lung and that a combination of thyroid transcription factor-1 and cytokeratin 20 is indicated to assist in the differentiation of metastatic small cell carcinoma of lung from merkel cell carcinoma.

Cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Report of a case and discussion of the origin of pseudoepitheliomatous hyperplasia.

We report a case of cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and may complicate the diagnosis of cutaneous melanoma. This diagnostic pitfall is important to both recognize and be cognizant of, so as to avoid diagnostic errors. The observation of the pseudoepitheliomatous hyperplasia, in this case with an extensive proliferation of eccrine ducts, provides further evidence that cutaneous pseudoepitheliomatous hyperplasia arises within the eccrine apparatus.

Hansen's disease in a patient with a history of sarcoidosis.

We report a rare case of concomitant Hansen's disease (HD) and sarcoidosis. Reticulin staining may be a helpful diagnostic tool in establishing the diagnosis of sarcoidosis in skin lesions. The diagnosis of HD can be established despite negative polymerase chain reaction results for the detection of Mycobacterium leprae DNA. Finally, a well-established diagnosis of sarcoidosis does not preclude the development of another granulomatous disorder. Hence, when new lesions developed in a patient with sarcoidosis despite appropriate therapy, other concurrent diagnoses should be pursued.

The use of chlorambucil with prednisone in the treatment of pemphigus.

BACKGROUND: Chlorambucil is an alkylating agent that preferentially affects B cells over T cells and has been shown to be effective in the treatment of bullous pemphigoid. OBJECTIVE: Our purpose was to determine whether chlorambucil is effective in the treatment of pemphigus. METHODS: We retrospectively reviewed the medical records of 9 patients with pemphigus (7 with pemphigus vulgaris and 2 with pemphigus foliaceus) in whom therapy with other immunosuppressive regimens failed and who were subsequently treated with chlorambucil and prednisone. RESULTS: There was clinical improvement in 6 of 9 patients and a decrease in indirect immunofluoresent antibody titers in 3 of the 5 patients who had titers drawn before and after treatment with chlorambucil. Three of the 9 patients failed treatment with chlorambucil, as evidenced by lack of improvement of lesions. CONCLUSION: Chlorambucil may be a potential adjuvant therapeutic approach with steroid-sparing effects in patients with pemphigus who have failed treatment with other immunosuppressive regimens.

Postoperative pressure-induced alopecia: report of a case and discussion of the role of apoptosis in non-scarring alopecia.

We report a case of postoperative pressure induced alopecia in a 21-year-old black female after multiple intraoperative procedures. The histopathology is distinctive and demonstrated features in common with trichotillomania and alopecia areata, including the presence of pigment casts, catagen follicles, melanophages and apoptotic bodies. External hair manipulation is considered the primary event in the etiology of pigment casts, however, our present case demonstrated numerous pigment casts despite a complete lack of evidence of external hair manipulation. We performed pattern analysis and in situ end-labeling in 19 cases of non-scarring alopecia. Pigment casts were seen in postoperative alopecia (1 case), alopecia areata (1 case) and trichotillomania (5 cases). These forms of alopecia have in common the sudden termination of the anagen phase of the hair cycle. When the anagen portion of the hair cycle is prematurely disrupted hairs enter into catagen. Pigment casts may represent a non-specific reaction pattern of follicles that are suddenly transformed from anagen to catagen. We therefore propose that hair manipulation is not uniquely responsible for the formation of pigment casts. The primary pathophysiology resulting in the formation of pigment casts more correctly reflects the sudden termination of the anagen phase of the hair cycle.

Behavior of tissue-engineered skin: a comparison of a living skin equivalent, autograft, and occlusive dressing in human donor sites.

OBJECTIVE: To compare the behavior of a tissue-engineered living skin equivalent (LSE) with an autograft in acute donor site wounds. DESIGN: Paired-comparison, randomized control trial. SETTING: A university dermatology service. PATIENTS: Three donor sites were created on the anterior thigh of each of 20 patients requiring split-thickness skin grafts. INTERVENTION: For each patient, the donor sites were randomly assigned to be treated with meshed LSE, meshed autograft, or a polyurethane film (PUF) occlusive dressing. Blood and biopsy samples were taken for immunologic and histological studies. MAIN OUTCOME MEASURES: Toxic effects or clinically apparent rejection, humoral and cellular immune responses, clinical take, healing time, pain, and 1-month histological appearance. RESULTS: There was no toxic effect or clinically apparent rejection of LSE. Results of humoral and cellular studies were unchanged from baseline. The average time to healing for LSE with clinical take was 7.3 days (SD, +/- 0.8 days); for autograft, 7.6 days (SD, +/- 1.1 days); and for PUF, 9.5 days (SD, +/- 1.8 days). The difference between LSE or autograft and PUF was statistically significant at the .001 level. Pain was experienced by 1 patient, no patients, and 10 patients at the LSE, autograft, and PUF sites, respectively. Histologically, LSE had the thickest epidermis (P = .02), PUF had the greatest degree of fibrosis (P = .02), and autograft had the least degree of increased inflammation (P = .004) and vascularity (P = .01). CONCLUSIONS: In acute donor site wounds, LSE appeared to clinically take and to be a safe and usable form of tissue therapy.

Bednar tumor (pigmented dermatofibrosarcoma protuberans) occurring in a site of prior immunization: immunochemical findings and therapy.

Bednar tumor is a rare pigmented variant of dermatofibrosarcoma protuberans (DFSP). Because of its rarity, information is lacking regarding the optimal therapy and potential utility of immunohistochemistry in diagnosis. We report a case of Bednar tumor in which the diagnosis was aided by immunohistochemistry for CD34, an antigen known to be expressed in DFSP but not previously reported in Bednar tumor. Our case was also striking because it represents the first reported appearance of a Bednar tumor at a site of prior immunization, a phenomenon previously noted in some cases of DFSP. The patient was treated effectively with Mohs surgery and is without recurrence at 9 months.