Jon H. Meyerle

Treatment of pyoderma gangrenosum with intravenous immunoglobulin

Background  Intravenous immunoglobulin (IVIG) is increasingly being used to treat inflammatory and autoimmune disease.

Alteration of skin properties with autologous dermal fibroblasts

Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

Bullous systemic lupus erythematosus: a review and update to diagnosis and treatment.

Bullous systemic lupus erythematosus (BSLE) is a rare cutaneous complication of systemic lupus erythematosus (SLE). It is a heterogeneous disease that is caused by autoantibodies to the dermoepidermal junction, mainly type VII collagen. Similarities in histology and immunopathology exist between BSLE and other primary bullous dermatoses, namely dermatitis herpetiformis (DH) and epidermolysis bullosa acquisita (EBA), respectively. EBA and BSLE commonly share the same autoantibody to type VII collagen and heterogeneous clinical presentations, creating a diagnostic challenge. However, clinical presentation combined with histology, immunological testing, and concomitant diagnosis of SLE distinguish this entity from other similar dermatoses. Diagnosis of this disease is important given its coexistence with SLE and its many complications. New developments in IgG subtyping have shown subtle variations in IgG subtypes between EBA and BSLE. In addition, rituximab was recently found to be efficacious in recalcitrant cases of BSLE that do not respond to dapsone and immunosuppressants. We review the topic of BSLE with emphasis on clinical, histologic, and immunopathologic features, as well as new methods of diagnosis and treatment.

Non-invasive estimation of skin thickness from hyperspectral imaging and validation using echography

BACKGROUND The skin is the largest organ and is subject to the greatest exposure to outside elements throughout one׳s lifetime. Current data by the American Academy of Dermatology suggests that approximately ten people die each hour worldwide due to skin related conditions. Cancers such as melanoma are growths that originate in the epidermis. Therefore, an accurate and non-invasive method to estimate skin constitutive elements can play an important clinical role in detecting the early onset of skin tumors. It can also serve as a valuable tool for research and development in cosmetics and pharmaceuticals in general. METHODS In our prior work, we developed a method that combined a physics-based model of human skin with machine learning and Hyperspectral imaging to non-invasively estimate physiological skin parameters, including melanosomes, collagen, oxygen saturation, and blood volume. In this work, we extend that model to also estimate skin thickness. Moreover, for the first time, we develop a protocol to test our methodology for skin thickness estimation using Ultrasound to acquire a gold standard dataset. RESULTS We tested our methodology for skin thickness estimation on a dataset of 48 Hyperspectral signatures obtained in vivo from six patients under IRB at Johns Hopkins Hospital. We found mean absolute errors on the order of the Ultrasound resolution (i.e., our gold standard). DISCUSSION This is the first study of its kind to validate skin thickness estimates using a gold standard. Our preliminary results constitute a proof-of-concept that hyperspectral-based methods can accurately and non-invasively estimate skin thickness in clinical settings.

High Prevalence of Stump Dermatoses 38 Years or More After Amputation

OBJECTIVE To highlight the prevalence and impact of skin disease at the stump site in patients who have undergone amputation. DESIGN A cross-sectional health questionnaire of Vietnam War veterans with stump dermatoses at least 38 years after major limb amputation. SETTING A research registry of veterans with combat-related amputations who agreed to participate. PARTICIPANTS Recruitment began January 1, 2006, and ended December 31, 2009, with a registry of 416 veterans. MAIN OUTCOME MEASURES Results of a self-reported 35-item questionnaire. Participants were later contacted by telephone or asked to complete a Web survey. RESULTS Of the 247 veterans, 119 (48.2%) reported at least 1 skin problem within the preceding year. The most common were skin breakdown (25.2%), rash (21.8%), and abrasion (21.0%). In addition, 25.2% experienced skin problems more than 50% of the time, and 37.1% had to alter or replace their prosthesis. Stump dermatoses limited or prevented prosthesis use in the preceding year for 55.6% and caused pain or discomfort at the stump site in 61.5%. CONCLUSIONS More than 38 years after major limb amputation, skin complications at the stump site continue to cause significant morbidities and contribute to prosthesis abandonment. The high prevalence of stump dermatoses stresses the importance of disease prevention, early management, and advanced treatment of skin disease.

Survey of Medical Student Preference for Simulation Models for Basic Dermatologic Surgery Skills: Simulation Platforms in Medical Education

BACKGROUND The authors investigated the use of simulator platforms in fourth‐year medical student education. OBJECTIVE To evaluate which simulation platform students preferred for learning dermatologic procedures and to assess the effectiveness of the exercise in terms of the change in confidence that the students had performing dermatologic procedures. MATERIALS AND METHODS After medical students were instructed on how to perform a punch biopsy and then assisted in executing the task, they were surveyed to determine their preferred simulation platform and simulator properties. Students were surveyed at the beginning and completion of the teaching block. RESULTS One hundred fifty‐seven students completed the skills laboratory, and 78 completed the preference questionnaire. Of the 11 surveyed categories, students preferred the pig foot in eight categories. Seventy students responded to a surgical skills questionnaire that assessed their overall confidence in planning and executing the procedure before and after the skills laboratory. The students had a statistically significant increase in confidence in dermatologic procedural skills as a result of the activity. CONCLUSION Preference data show that the pig foot model is preferred for teaching dermatologic surgical skills. These results re‐affirm that the pig foot model is an effective, low‐cost solution for training.

Bullous Lupus in an 18‐Year‐Old

To the Editor: We read with interest the article by Tincopa et al (1) regarding a 13-year-oldAfricanAmerican girl presenting with bullous systemic lupus erythematosus. We have recently diagnosed another case of bullous systemic lupus erythematosus in a teenage girl that we would like to share. An 18-year-old African American girl presented to our dermatology clinic with a 3-week history of a vesicular eruption involving the oral mucosa, face, posterior auricular area, trunk, and buttocks. Per patient report, the vesicles began over her trunk and buttocks and progressed to include her face and mouth. The patient also reported a 3-month history of fatigue, arthralgia, and myalgia. On examination, she appeared tired. She had multiple 2to 3-mm tense, fluid-filled vesicles over her bilateral cheeks, chin, posterior auricular area, and vermillion lip as well as erosions of her oral mucosa. Lesions on her trunk and buttocks had largely resolved, some replaced by crusting, others with residual postinflammatory hyperpigmentation. The patient had no significant past medical history and was taking no medications at the time of presentation. Family history was unremarkable for autoimmune diseases. Laboratory analyses at initial presentation were notable for an erythrocyte sedimentation rate of 79 mm ⁄hour and C-reactive protein of 2.656 mg ⁄dL. Complete blood count was notable for hemoglobin of 9.6 g ⁄dL and hematocrit of 29.5%. Direct antiglobulin test was positive for hemolytic anemia. Urinalysis was unremarkable.Her antinuclear (ANA), double-stranded DNA, Smith, SCL-70, ribonucleoprotein, Jo-1, SS-A, and SS-B antibody panels were negative. Complement C3 and C4 were both low (51.8 mg ⁄dL and 7.4 mg ⁄dL, respectively). Viral cultures of vesicle fluid were negative for herpes simplex 1 and 2 and varicella zoster. Initial skin biopsies were obtained from the vermillion lip for hematoxylin and eosin (H&E) and direct immunofluorescence (DIF). Histology revealed a cell-poor subepidermal split; DIF revealed only granular deposition of C3 in the superficial and mid-dermal vessels. Because of high clinical suspicion, ANAwas repeated 1 week later and found to be positive at a titer of 1:640. Biopsies for H&E and DIF were also repeated, this time from the left cheek. The H&E was notable for subepidermal clefting, scant neutrophils, and abundant mucin deposition. DIF demonstrated a broad ribbon-like pattern along the dermal–epidermal junction for immunoglobulin (Ig)G, IgA, IgM, and C3; salt-split skin was positive for IgG, IgA, and IgMon the floor of the blister. A diagnosis of bullous lupus erythematosus was made, and the patient was started on prednisone 40 mg daily (1mg ⁄kg per day) and hydroxychloroquine 200 mg daily, which resulted in improvement of her fatigue, but she continued to develop new blisters. We are planning to admit her next week for intravenous immunoglobulin and pulse-dosed solumedrol. We feel this presentation of bullous lupus further supports Tincopa et al’s conclusion to consider this diagnosis in the evaluation of vesiculobullous eruptions in the pediatric population andmaintain a low threshold for biopsy and repeat laboratory evaluation if felt appropriate.

An examination of TNM staging of melanoma by a machine learning algorithm

Accurate estimation of mortality in patients with cancer is important when discussing prognosis and selecting treatment. Survival estimation for many cancers is based on Tumor-Node-Metastasis (TNM) staging systems that involve three factors: tumor extent, lymph node involvement, and metastasis. The most recent clinical staging of melanoma uses TNM staging but does not include a growing number of other prognostic features. The Ensemble Algorithm of Clustering of Cancer Data (EACCD) by Chen et al. is a machine learning algorithm that regroups patients with different prognostic factors according to the survival dissimilarity. This algorithm has the potential to integrate emerging prognostic factors to more accurately stage melanoma. In this study, we use EACCD to examine the current AJCC staging of melanoma by analyzing a melanoma dataset from the National Cancer Centers Surveillance, Epidemiology, and End Rresults (SEER) database. Our results demonstrates that the EACCD algorithm generates results in-line with AJCC staging and may provide a mechanism to incorporate other prognostic factors to produce a more nuanced estimation of prognosis and survival.

An outbreak of urticaria among soldiers deploying for combat

An outbreak of urticaria among soldiers deploying for combat Dear Sir, Before deploying overseas, American military personnel receive a battery of vaccinations specific for their destination. Rabies human diploid cell vaccine (HDCV), Imovax® (Aventis Pasteur, Strasbourg, France), is administered to certain troops en route to Africa and Asia where rabies is common in feral animals and the troops do not have ready access to health care. Although adverse reactions to rabies HDCV are uncommon, 1 we report an outbreak of rabies HDCV-associated urticaria in a unit deploying for combat. A 42-year-old man developed generalized pruritus with scattered edematous red wheals over his trunk and swelling of his right upper eyelid. He had received the second immunization in the series of the rabies HDCV 14 days earlier. On examination, he was noted to have clearly defined blanching, edematous, red plaques with no evidence of petechiae, purpura, peripheral edema or lymphadenopathy. He denied fevers or arthralgias. We examined 12 additional men who over the previous few days had presented to medical personnel with similar complaints. The interval from receiving the HDCV immunization to the onset was urticaria was 5–15 days. Six patients received treatment with oral antihistamines with or without prednisone and all cases resolved without sequelae. We recently investigated an outbreak of urticaria in 13 soldiers at a processing center for overseas deployment. The 13 men all shared the common cutaneous finding of urticaria. These 13, along with 305 other soldiers in their group, had received a booster dose of the rabies HDCV or the second or third doses in the 3-dose pre-exposure series. The overall rate of urticaria was 4.3%. No other noteworthy adverse reactions were reported. The standard rabies vaccine series consists of three 1.0-ml intramuscular doses of rabies HDCV given on days 0, 7 and either 21 or 28. 2 The Advisory Committee on Immunization Practices recommends booster vaccination at 6 months or 2 years depending on the exposure risk and serologic status. Urticarial reactions to rabies HDCV occur more frequently after the booster rather than the primary immunization. 1 The reported incidence of urticaria in patients receiving the rabies HDCV ranges from 2 to 7%. 1,3 They are thought to represent a Type III hypersensitivity-mediated immune response rather than a Type 1 IgE-mediated event. 3 Skin biopsies from rabies HDCV-associated urticarial lesions often demonstrate a leukocytoclastic vasculitis with neutrophil and lymphocytic infiltrates; fibrin and C1q granular deposits may be found on direct immunofluorescence. 3 Although, histological findings support the presence of immune complex-mediated urticaria, there is no laboratory evidence (proteinuria, elevated creatinine or blood urea nitrogen) of renal or other systemic involvement. In this outbreak of HDCV-associated urticaria, none of the patients had clinical evidence of serum sickness; however, no laboratory investigations were performed. Because HDCV is rarely administered to large cohorts of individuals, an outbreak such as this one has not been reported previously.

The Use of Apremilast to Treat Psoriasis During Deployment

Psoriasis is a chronic immune-mediated dermatologic disorder affecting approximately 2% of the general population. Under current U.S. Army regulation, the diagnosis of psoriasis is a bar to enlistment or appointment and, if poorly controlled, is grounds for referral to a Medical Evaluation Board and potential discharge from military service, according to Army Regulation 40-501. However, between 2008 and 2015, over 3,600 soldiers sought care for psoriasis while deployed to combat theaters, indicating that psoriasis remains a significant medical concern in the U.S. military. Although mild psoriasis is treatable with topical agents, moderate to severe psoriasis may require systemic treatment. Prior to Food and Drug Administration approval of apremilast (Otezla) in 2014, the standard systemic treatment options were methotrexate and biologic agents such as anti-Tumor Necrosis Factor-alpha medications. Active use of methotrexate or biologic immunomodulatory medications automatically disqualifies soldiers from deployment due to monitoring requirements, the need for refrigeration, and the risk for immune compromise. Apremilast offers treatment efficacy similar to that of methotrexate, and it may be taken while deployed because it does not require monitoring or refrigeration. However, efficacy must be evaluated in the context of its much higher unit cost. Nonetheless, we argue that apremilast may be a useful treatment option for psoriasis in a select group of soldiers who must deploy despite suffering from moderate to severe psoriasis.