Misha Rosenbach

Diverse cutaneous side effects associated with BRAF inhibitor therapy: A clinicopathologic study

BACKGROUND Vemurafenib, a novel selective small molecule inhibitor of BRAF, has recently been shown to be effective in the treatment of melanomas harboring the BRAF V600E mutation. Similar to the broad-spectrum RAF inhibitor sorafenib, vemurafenib induces development of squamous cell carcinomas and keratoacanthomas as a side effect of therapy. OBJECTIVE We sought to detail additional cutaneous adverse effects of vemurafenib and a similar BRAF inhibitor, dabrafenib. METHODS We evaluated the clinical and histologic feature of skin side effects developing on vemurafenib or dabrafenib therapy in 14 patients. RESULTS Eight patients developed one or more squamous cell carcinomas, and 11 patients formed benign verrucous keratoses. Eight patients developed single lesions and/or widespread eruptions with histopathologic findings of acantholytic dyskeratosis, consistent with warty dyskeratomas and Darier- or Grover-like rashes, respectively. One patient developed palmoplantar hyperkeratosis, and darkening of existing nevi and new nevi within 2 months of starting vemurafenib. Side effects presented as early as 1 week after beginning therapy, with a mean time of onset of 12.6 weeks in our cohort. LIMITATIONS This study was limited by the small number of cases, all from a single institution. CONCLUSION Selective BRAF inhibitor therapy is associated with the development of malignant and benign growths, including keratoacanthoma-like squamous cell carcinomas, warty dyskeratomas, and verrucous keratoses, along with widespread eruptions with histologic features of acantholytic dyskeratosis. Given the potential for malignant lesions to develop on treatment, awareness of potential adverse effects of these agents is necessary, and a low threshold for biopsy of new growths is recommended.

Reliability and Convergent Validity of Two Outcome Instruments for Pemphigus

A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here, we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physicians Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95% confirdence interval (CI)=0.61-0.91) for the PDAI and 0.77 (0.63-0.91) for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 (0.17-0.60) for the ABSIS and 0.86 (0.76-0.95) for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 (0.96-1.0) for the PDAI and 0.80 (0.65-0.96) for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild-to-moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS.

Tumor necrosis factor-inhibitor associated dermatomyositis

BACKGROUND Dermatomyositis is an autoimmune disease of unknown etiology characterized by inflammation of the skin and muscles. Several medications have been implicated in the development of dermatomyositis; however, the disease has rarely been linked to the use of tumor necrosis factor (TNF) inhibitors. We report 4 cases of dermatomyositis that developed or were exacerbated by exposure to the TNF inhibitors etanercept and adalimumab. Observation Four patients with symptoms of inflammatory arthritis were treated with TNF inhibitors for a duration ranging from 2 months to 2 years. All 4 patients developed symptoms consistent with dermatomyositis, including inflammatory rash and muscle weakness. Their symptoms persisted after discontinuation of the treatment with the TNF inhibitors but responded to treatment with corticosteroids and immunosuppressive medications. CONCLUSIONS Tumor necrosis factor inhibitors have been associated with the onset of a number of autoimmune disorders, most commonly vasculitis and a lupuslike syndrome. Rarely have they been associated with dermatomyositis. The 4 cases reported herein indicate that TNF inhibitor use can be associated with either induction or exacerbation of dermatomyositis.

Treatment of erythrodermic psoriasis: From the medical board of the National Psoriasis Foundation

BACKGROUND Erythrodermic psoriasis is a severe form of psoriasis that can arise acutely or follow a chronic course. There are a number of treatment options, but overall there are few evidence-based data to guide clinicians in managing these challenging cases. OBJECTIVE Our aim was to create treatment recommendations to help dermatologists treat patients with erythrodermic psoriasis. METHODS A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for erythrodermic or exfoliative psoriasis. Meetings were held by teleconference and were coordinated and funded by the National Psoriasis Foundation. Consensus on treatment of erythrodermic psoriasis was achieved. A literature review was conducted to examine treatment options for erythrodermic psoriasis and the strength of the evidence for each option. RESULTS There is no high-quality scientific evidence on which to base treatment recommendations. Treatment should be dictated by the severity of disease at time of presentation and the patients comorbidities. Cyclosporine and infliximab appear to be the most rapidly acting agents for the treatment of erythrodermic psoriasis. Acitretin and methotrexate are also appropriate first-line choices, although they usually work more slowly. Treating physicians can consider a number of second-line agents, including etanercept or combination therapy, in the treatment of patients with erythrodermic psoriasis. Combination therapy may be more effective than a single-agent approach; there is a paucity of scientific data in this area. All patients should be evaluated for underlying infection. Supportive care can help control disease and patient symptoms if instituted appropriately. Physicians should avoid potential exacerbating agents when managing this challenging disease. LIMITATIONS There are few high-quality studies examining treatment options for erythrodermic psoriasis. CONCLUSION Treatment of patients with erythrodermic psoriasis demands a thorough understanding of the treatment options available. Therapy should be based on acuity of disease and the patients underlying comorbidities. There are limited data available to compare treatment options for erythrodermic psoriasis. Further studies are necessary to explore the optimal treatment algorithm for these patients.

Donor-derived Strongyloides stercoralis infections in renal transplant recipients

Background. Donor-derived Strongyloides stercoralis infection occurs rarely after transplantation, and the risk factors are not well understood. We present cases of two renal allograft recipients who developed Strongyloides hyperinfection syndrome after receipt of organs from a common deceased donor who received high-dose steroids as part of a preconditioning regimen. Methods. The two renal transplant patients who developed Strongyloides hyperinfection syndrome are reported in case study format with review of the literature. Results. Microscopic examination of stool from one renal transplant patient and of tracheal and gastric aspirates from the other transplant patient revealed evidence of S. stercoralis larvae. Retrospective testing of serum from the deceased donor for Strongyloides antibodies by enzyme-linked immunosorbent assay was positive at 11.7 U/mL (Centers for Disease Control reference >1.7 U/mL positive). One patient was treated successfully with oral ivermectin. The other patient also had complete resolution of strongyloidiasis, but required a course of parenteral ivermectin because of malabsorption from severe gastrointestinal strongyloidiasis. Conclusions. These case studies provide some of the best evidence of transmission of S. stercoralis by renal transplantation. Because of the high risk of hyperinfection syndrome and its associated morbidity and mortality, high-risk donors and recipients should be screened for Strongyloides infection, so that appropriate treatment can be initiated before the development of disease. This study indicates that parenteral ivermectin can be used safely and effectively in patients in whom severe malabsorption would preclude the effective use of oral formulation. These cases also suggest that reconsideration should be given for the safety of steroids in donor-preconditioning regimens.

Lenalidomide for the Treatment of Resistant Discoid Lupus Erythematosus

BACKGROUND Discoid lupus erythematosus (DLE) is a chronic, disfiguring disease that is characterized by scaly, erythematous, disk-shaped patches and plaques followed by atrophy, scarring, and dyspigmentation. It is refractory to standard therapies in a small population of patients. We investigated the use of lenalidomide, a thalidomide analogue, as a novel alternative therapy in 2 cases of refractory DLE and report our results. OBSERVATIONS Two patients with chronic, severe DLE were treated with low-dose lenalidomide. Improvement was noted within 1 month at a dosage of 5 mg/d in one case and was maintained for 10 months before the dosage was doubled to 10 mg/d for 12 months because of a slight worsening of symptoms. Clinical improvement was demonstrated by a sustained reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score, with no change in the Cutaneous Lupus Erythematosus Disease Area and Severity Index damage score. Within 5 months, oral prednisone therapy (60 mg/d) was tapered and discontinued; it was restarted at a low dosage (5 mg/d), however, to manage the symptoms of systemic LE. Of note, the patient experienced mild neutropenia after taking 10 mg/d of lenalidomide, which carries a black box warning regarding neutropenia; therefore, the complete blood cell count should be monitored weekly for the first 2 months and then monthly thereafter. The second case failed to show clinical improvement, and lenalidomide therapy was discontinued after 6 months. CONCLUSIONS Lenalidomide therapy is a potential alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. A larger study is needed to clarify its role in the treatment of DLE and other forms of cutaneous LE.

The histopathologic spectrum of decorative tattoo complications

Tattooing for ornamental purposes is an ancient practice that remains popular in modern times. Tattoos are encountered by the dermatopathologist either as incidental findings on skin biopsies or because of complications specific to the tattoo. A range of neoplasms and inflammatory conditions are seen in association with tattoos, many of which may be attributed to hypersensitivity to tattoo inks. The composition of tattoo inks is highly variable, and inks can contain numerous potentially allergenic or carcinogenic compounds. Infections with bacterial, viral and fungal species can occur after tattooing, sometimes after substantial delay. Atypical mycobacterial infections in particular are increasingly reported; special stains for mycobacteria should be performed and cultures recommended particularly when dense, mixed or granulomatous infiltrates are present.

The Reliability of Teledermatology to Triage Inpatient Dermatology Consultations

IMPORTANCE Many hospitals do not have inpatient dermatologic consultative services, and most have reduced availability of services during off-hours. Dermatologists based in outpatient settings can find it challenging to determine the urgency with which they need to evaluate inpatients when consultations are requested. Teledermatology may provide a valuable mechanism for dermatologists to triage inpatient consultations and increase efficiency, thereby expanding access to specialized care for hospitalized patients. OBJECTIVE To evaluate whether a store-and-forward teledermatology system is reliable for the initial triage of inpatient dermatology consultations. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 50 consenting adult patients, hospitalized for any indication, for whom an inpatient dermatology consultation was requested between September 1, 2012, and April 31, 2013, at the Hospital of the University of Pennsylvania, an academic medical center. The participants were evaluated separately by both an in-person dermatologist and 2 independent teledermatologists. MAIN OUTCOMES AND MEASURES The primary study outcomes were the initial triage and decision to biopsy concordance between in-person and teledermatology evaluations. RESULTS Triage decisions were as follows: if the in-person dermatologist recommended the patient be seen the same day, the teledermatologist agreed in 90% of the consultations. If the in-person dermatologist recommended a biopsy, the teledermatologist agreed in 95% of cases on average. When the teledermatologist did not choose the same course of action, there was substantial diagnostic agreement between the teledermatologist and the in-person dermatologist. The Kendall τ rank correlation coefficients for initial triage concordance between the in-person dermatologist and teledermatologists were 0.41 and 0.48. The Cohen κ coefficients for decision to biopsy concordance were 0.35 and 0.61. The teledermatologists were able to triage 60% of consultations to be seen the next day or later. The teledermatologists were able to triage, on average, 10% of patients to be seen as outpatients after discharge. CONCLUSIONS AND RELEVANCE Teledermatology is reliable for the triage of inpatient dermatology consultations and has the potential to improve efficiency.

Viral-Associated Trichodysplasia: Characterization of a Novel Polyomavirus Infection With Therapeutic Insights

BACKGROUND Viral-associated trichodysplasia of immunosuppression is a rare cutaneous eruption that is characterized by follicularly based shiny papules and alopecia with characteristic histopathologic findings of abnormally anagen follicules with excessive inner root sheath differentiation. Prior reports have described the histopathologic characteristics on vertical sections; however, to our knowledge, immunohistochemical analysis of polyomavirus proteins has not been previously performed. OBSERVATIONS We discuss the thorough diagnostic evaluation and therapy of an unusual case of viral-associated trichodysplasia due to a newly described human polyomavirus that occurred in a patient with posttreatment chronic lymphocytic leukemia and an abnormal white blood cell count. Unique to our study is the immunohistochemical staining for the polyomavirus middle T antigen, which demonstrated positive staining of cellular inclusions within keratinocytes that compose the inner root sheath. Further evaluation with scanning electron microscopy and polymerase chain reaction analysis of viral DNA confirmed the presence of the virus. Treatment with topical cidofovir resulted in dramatic clinical improvement and hair regrowth. CONCLUSIONS Several tools, including immunohistochemical staining for the polyomavirus middle T antigen, can be used to identify the pathogenic virus associated with viral-associated trichodysplasia. This case highlights the utility of multiple diagnostic modalities and a robust response to a topical therapeutic agent, cidofovir.

Neutrophilic Dermatoses: An Update

Neutrophilic dermatoses constitute a heterogeneous group of dermatologic diseases, which are unified by the predominance of neutrophils within the inflammatory infiltrate on histopathology. The aims of this review were to provide an update on the clinical and histologic presentation of the main neutrophilic dermatoses and to develop a guide for clinical practice. A structured literature search of PubMed, Medline, and Embase was performed, using the key words “neutrophilic disorders”, “cutaneous small vessel vasculitis”, “Sweet’s syndrome”, “bowel associated dermatosis arthritis syndrome”, “Behcet’s”, “palisaded neutrophilic and granulomatous dermatosis”, “rheumatoid neutrophilic dermatitis”, and “pyoderma gangrenosum”. Related articles were screened for key terms and were included if appropriate. This group contains a wide spectrum of unique disorders, each with its own histologic and clinical subtleties, making specific diagnosis of a given entity within the group diagnostically challenging. The fact that overlapping forms of neutrophilic dermatoses, which share features of multiple neutrophilic dermatoses, are not uncommon makes the diagnoses more challenging.