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.

Cloning of the 5' mRNA for the 230-kD bullous pemphigoid antigen by rapid amplification of cDNA ends.

The 230-kD bullous pemphigoid antigen (BPAG1), defined by autoantibodies in patient sera, is a hemidesmosomal plaque protein in the same gene family as the intracellular proteins desmoplakin I/II and plectin. We had previously isolated, from a lambda gt11 library, overlapping cDNA clones with 6921 bp of mRNA sequence for BPAG1. The coding sequence encoded by these clones included the 3' stop codon but not the 5' coding and non-coding region of the mRNA. To obtain these sequences we used the polymerase chain reaction (PCR) method called rapid amplification of cDNA ends (RACE). The PCR products were cloned into plasmids and sequenced. With five PCR primers we were able to obtain overlapping clones containing the 5' region of the mRNA. An upstream stop codon in frame with the rest of the coding sequence demonstrates that the full 5' coding sequence is obtained. Four different PCR products from two separate reactions had the same 5' end, suggesting that this 5' end is near, or at, the transcription start site. No alternatively spliced clones were found and no transmembrane site was predicted, confirming that BPAG1 is an intracellular hemidesmosomal plaque protein.

Southern analysis of the 230-kD bullous pemphigoid antigen gene in normal humans, animals, and patients with junctional epidermolysis bullosa.

To begin to characterize the 230-kD bullous pemphigoid antigen (BPA) gene, we performed Southern analysis on genomic DNA with probes derived from 7 kb of cDNA that spans most of the coding region of this hemidesmosomal plaque protein. When hybridized to a 1-kb fragment of this BPA cDNA, normal human genomic DNA digested with EcoRI, BamHI, PstI, HindIII, or EcoRV showed only a single band, which was unique for each enzyme, indicating a single human gene for BPA. To determine if a related gene exists in animals, we used probes covering the full 7 kb of cDNA for Southern analysis of genomic DNA from various vertebrates. A related gene was detected in other mammals (monkey, cow, dog, rabbit, mouse, and rat) but not in chicken, frog, or fish. Under these same hybridization conditions a probe for human beta-actin could detect an actin gene in all these species. Furthermore, immunofluorescence showed that an antibody raised against portions of the 230-kD BPA bound to the epidermal basement membrane of mammals but not that of a bird or amphibian. Finally, because most patients with junctional epidermolysis bullosa (JEB) have defective hemidesmosomes in ultrastructure, and probably function, we analyzed genomic DNA from these patients. No restriction fragment length polymorphisms (RFLP) were detected when the DNA from 11 normals and 8 JEB patients (representing 16 possible defective genes) was digested with BamHI, EcoRI, or PstI and hybridized to any part of the cDNA. These findings indicate that 1) there is a single BPA gene in humans; 2) a closely related gene exists in other mammals but not birds, amphibia, or fish; and 3) gross abnormalities of the BPA gene are not characteristic of JEB patients.

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.

Ant, bee, and wasp stings.

Stinging insect envenomation and allergy remain important clinical and research problems. Approximately 40 deaths occur annually as a result of these stings. The dermatologist can help to avoid this outcome by appropriate recognition of the offending insect and by instituting or arranging the appropriate therapy and avoidance. Bee-sting kits should be encouraged for sensitive individuals. Dermatologists should be alert to the increasing imported fire ant problem, be able to make the diagnosis, and help the patient recognize and avoid these pesky arthropods.

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.

Chromoblastomycosis.

Chromoblastomycosis is a chronic cutaneous infection due to several varieties of pigmented fungi. Diagnosis is straightforward and based on clinical and microscopic findings. Despite the protracted course of the disease, dissemination of the infection is rare. New insights into the pathophysiology may permit a closer appreciation of the clinical course. Treatment in advanced cases is difficult and frequently requires extensive surgery or lengthy therapy with physical or medical approaches.

Comparative structural analysis of desmoplakin, bullous pemphigoid antigen and plectin: members of a new gene family involved in organization of intermediate filaments.

Desmoplakins (DP) and bullous pemphigoid antigen (BPA) are major plaque components of the desmosome and hemidesmosome, respectively. These cell adhesion structures are both associated intimately with the intermediate filament (IF) network. Structural analyses of DP and BPA sequences have indicated that these molecules are likely to form extended dumbbell-shaped dimers with a central rod and globular end domains. Recent sequence data have indicated that the N-terminal domains of both DP and BPA (like their C-terminal domains) are highly related: the former contain regions of heptad repeats that are predicted to form several alpha-helical bundles. Comparisons of DP and BPA protein sequences with that of plectin (PL), a 466 kDa IF-associated protein, have also revealed large scale homology. Identities between their N-terminal domains are: DP:BPA = 35%, DP:PL = 32%, BPA:PL = 40%, suggesting that BPA is more closely related to PL than DP in this region. In the C-terminal domains, which contain a 38-residue repeating motif, however, DP and PL are closer relatives (identities: DP:BPA = 38%, BPA:PL = 40%, DP:PL = 49%). The central domains of all three proteins have extensive heptad repeat substructure, express the same periodic distribution of charged residues, and are predicted to form two-stranded alpha-helical coiled-coil ropes. These observations suggest that DP, BPA and PL belong to a new gene family encoding proteins involved in IF organization.

Routine histologic examination for the diagnosis of onychomycosis: an evaluation of sensitivity and specificity.

Clinical differentiation of dermatophyte infection from dystrophic changes due to psoriasis may be challenging. Typically, potassium hydroxide (KOH) preparations, fungal culture, and occasionally, nail unit biopsy specimens are utilized to help differentiate between the two. These tests are often time-consuming and may yield false-negative results. Increasing regulation of the office laboratory has caused some physicians to forgo this testing, which was previously routine. We investigated the utility of routine histologic examination of nail clippings in differentiating onychomycosis from psoriatic onychodystrophy. Twenty-three distal nail clipping specimens (twelve specimens from patients with onychodystrophy of unknown cause and eleven control specimens from nails with known cause) were evaluated by routine histology and periodic acid-Schiff (PAS) staining. Of the dystrophic cases, four were demonstrated to be onychomycosis by the presence of hyphae on histologic evaluation and by culture, whereas only three of these cases yielded positive results on KOH examination. Eight cases of onychodystrophy were due to psoriasis. Yeast forms were detected on one case of psoriatic onychodystrophy that demonstrated yeast growth on culture. In our study, routine histologic examination with PAS staining was equal to culture and superior to KOH preparation in leading to the correct diagnosis of dermatophyte infection. In addition, the diagnosis of psoriasis of the nail plate was detected accurately by routine histologic examination. Routine histologic examination with PAS staining is a rapid, simple, and reliable test in the evaluation of onychodystrophy.

Congenital midline hamartoma: case report with histochemical and immunohistochemical findings.

We report the case of a polypoid nodule on the chin of an infant. Microscopically, the lesion featured numerous pilosebaceous units, eccrine sweat glands, arrectores pilorum muscles, mature adipose tissue, and prominent admixtures of skeletal muscle. This lesion has much in common with the accessory tragus, and is similar to the one reported earlier as rhabdomyomatous mesenchymal hamartoma. We feel the more general term congenital midline hamartoma is preferable, as it encompasses both the clinical and microscopic features of the lesion.

Cutaneous metastasis from papillary carcinoma of the thyroid gland.

Cutaneous metastases from carcinoma of the thyroid gland are rare. We present the clinical, histologic, and immunohistochemical features of a solitary metastasis from papillary carcinoma of the thyroid. Our results indicate that this tumor can produce epithelial mucin and, therefore, must be differentiated from other metastatic carcinomas and from primary apocrine tumors of the skin. Positive staining for thyroglobulin confirmed the diagnosis in this case.

Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum.

BACKGROUND: Recombinant human interferon beta-1b has been recently approved for the treatment of multiple sclerosis. A significant proportion of patients treated with this medication experienced cutaneous reactions. OBJECTIVE: We describe the clinical and histologic features of cutaneous reactions to recombinant human interferon beta-1b. METHODS: Consecutive patients with cutaneous reactions to recombinant interferon beta-1b were evaluated clinically and by biopsy. RESULTS: Clinical lesions varied from subtle uninflamed sclerotic dermal plaques to erythematous plaques to cutaneous ulcers at injection sites. The nonsclerotic lesions were frequently painful. The firm plaques showed fibrosis histologically, whereas nonsclerotic inflammatory lesions demonstrated a consistent pattern of vascular thrombosis. Hematologic evaluation demonstrated platelet activation in most patients with inflammatory lesions, a feature also noted before interferon treatment in some patients. CONCLUSION: Therapy with recombinant interferon beta-1b is associated with a spectrum of cutaneous reactions and vascular thrombosis.

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.

Dermatopathology via a still-image telemedicine system: diagnostic concordance with direct microscopy.

OBJECTIVE: To determine the concordance of dermatopathology diagnosis by still-image telemedicine technology and direct microscopy. MATERIALS AND METHODS: Skin specimens (N = 79) were examined by a dermatopathologist using a still-image phone system, and the diagnoses were compared with those made by the same dermatopathologist 1 year earlier by direct microscopy. The telemedical diagnoses were reached first without, and then with, patient histories. RESULTS: When the patient history was available, identical diagnoses were made in 66 of the 79 cases (84% concordance rate). Without patient history, the concordance rate was 80%. The diagnostic concordance rate for the diagnosis of benign nevocytic nevi, inflammatory diseases, and benign and malignant non-squamous cell carcinoma neoplasms was statistically significantly greater than the concordance rate for the diagnosis of squamous cell carcinoma and squamous cell carcinoma in situ (P = 0.005). CONCLUSIONS: The diagnostic concordance rate achieved by teledermatopathology using a still-image phone system fell short of the 99% intraobserver diagnostic concordance rate using direct microscopy.

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.