Lindsay C. Strowd

Therapeutic ladder for pemphigus vulgaris: Emphasis on achieving complete remission

BACKGROUND Pemphigus vulgaris (PV) is a blistering autoimmune bullous disease that is usually fatal without proper treatment. There are no clear treatment guidelines for PV at this time. PURPOSE We suggest a standard treatment regimen for patients with PV based on the success of our treatment. METHODS A retrospective chart review of 18 patients with PV was conducted to assess response to a similar approach using mycophenolate mofetil (MMF) and prednisone. Diagnosis was confirmed through routine histology, direct immunofluorescence, and indirect immunofluorescence, and patients were followed up for a total average of 35.2 months. RESULTS We achieved complete disease control in 89% of patients using our treatment algorithm. Fourteen of 18 patients achieved complete disease control on therapy with prednisone and MMF. Three of the 4 patients who did not achieve control on MMF and prednisone went on to receive rituximab therapy, and two of those patients achieved disease control on rituximab. The average length of time from initiating therapy to 75% clearance of lesions was 4.5 months. Three of 18 patients were able to discontinue therapy after an average of 3 years and have remained in complete remission for more than 1 year. LIMITATIONS This was a retrospective chart review with a small patient sample size. CONCLUSIONS The combination therapy of MMF and prednisone is an effective treatment regimen to achieve rapid and complete control of PV. For those patients who fail treatment with MMF and prednisone, rituximab is an efficacious alternative therapy.

Dysphagia dietary guidelines and the rheology of nutritional feeds and barium test feeds.

BACKGROUND Dysphagia can lead to aspiration of oral feeds, thus causing pneumonia. Dysphagia is diagnosed by assessing the ability to swallow barium test feeds (BTF) of different viscosities. Dysphagia diet foods (DDF) are thickened as recommended by the National Dysphagia Diet (NDD) guidelines. To our knowledge, there are no published data evaluating if the viscosity of BTF or commercial DDF meet NDD guidelines. METHODS A TA1000 rheometer (TA Instruments; New Castle, DE) measured dynamic viscosity of BTF and DDF using creep transformation under controlled stress. Thin DDF studied included Plus Energy Drink (Boost; Novartis/Nestle; Fremont, MI) and Instant Breakfast (Carnation; Wilkes-Barre, PA) and nectar- and honey-thick DDF from Hormel (Hormel Health Labs; Savannah, GA) and Novartis (Novartis/Nestle). The BTF studied were thin, nectar-, and honey-thick Polibar barium suspension or Varibar (E-Z-EM, Inc.; Lake Success, NY). We measured batch-to-batch variability in the viscosity of DDF, with and without shaking, and after 2 h at ambient temperature at a shear rate chosen to match natural swallowing. RESULTS We observed the following: (1) DDF: the viscosity of honey-thick DDF was consistent with NDD guidelines, but other products were not. All products had minimal change in viscosity over 2 h. Boost thin liquid had > 300% increase in viscosity after shaking. (2) BTF: thin barium had a viscosity consistent with NDD guidelines. The nectar- and honey-thick Polibar BTFs were thixotropic and had unacceptably high viscosity. Varibar BTFs were not thixotropic but were more viscous than the NDD guidelines. CONCLUSIONS There was a poor relationship between the viscosity of DDF and BTF. The viscosity of BFTs is much greater than the correspondingly named diet foods and the NDD guidelines. This can place patients at significant risk for oral aspiration.

Increasing use of more potent treatments for psoriasis

BACKGROUND Psoriasis therapy has evolved during the past 25 years as newer and more effective medications become available. Furthermore, various combination regimens and approaches have been advocated. OBJECTIVE We sought to describe patterns of psoriasis treatment from 1986 to 2005. METHODS Visits to dermatologists for treatment of psoriasis were identified using National Ambulatory Medical Care Survey data, a representative survey of visits to physician offices in the United States. We focused on medications listed at these visits during the 1986-to-2005 interval to determine how treatment for psoriasis has changed. RESULTS There were an estimated 23.9 million visits for psoriasis during the 20-year study period. As a category, the most common medications used for psoriasis were topical steroids. Dermatologists are prescribing more potent topical steroids compared with nondermatologists. The use of these potent drugs has increased from 1986 to 2005. There has been growing use of systemic treatments, with biologic therapies introduced in the 2001-to-2005 time period. LIMITATIONS National Ambulatory Medical Care Survey data represent national trends in psoriasis treatment and cannot be used to evaluate smaller subpopulations of patients with psoriasis. These data are used to speculate why certain trends in treatment are seen. CONCLUSION The primary treatment for psoriasis in the late 1980s and early 1990s was mid-potency corticosteroids. Since then, the primary therapies for psoriasis have evolved to include class I ultrapotent topical corticosteroids, vitamin-D analogs, and systemic medications such as methotrexate and biologic agents. These changes in psoriasis management are consistent with patient desire for better disease control.

Quality of Life of Patients With Pyoderma Gangrenosum and Hidradenitis Suppurativa

Background: Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are painful and unsightly dermatologic disorders that have the potential to significantly decrease patients’ quality of life (QOL). Due to the difficulties associated with curing these conditions, QOL improvement is imperative. Objective: To determine if there are PG and HS disease-specific QOL measures and to assess whether QOL is being systematically studied in clinic populations or clinical trials. Methods: A PubMed search was performed to identify QOL studies for patients with PG and HS. Sources from other papers were also utilized. Results: QOL is rarely qualitatively or quantitatively assessed in HS and PG studies. We identified no validated disease-specific QOL measures for either PG or HS. Conclusion: Development of disease-specific QOL indices, clinical use of QOL measurement tool, and formal QOL evaluation in clinical trials would help to define the impact of PG and HS treatment in patients’ lives.

Epidemiology, Diagnosis, and Treatment of Scabies in a Dermatology Office

Background: Scabies is a neglected skin disease, and little is known about current incidence and treatment patterns in the United States. The purpose of this study was to examine demographic data, treatment types, success of treatment, and misdiagnosis rate of scabies in an outpatient dermatology clinic. Methods: A retrospective chart review of patients diagnosed with scabies within the past 5 years was performed. Results: A total of 459 charts were identified, with 428 meeting inclusion criteria. Demographic data, diagnostic method, treatment choice, misdiagnosis rate, treatment failure, and itching after scabies are also reported. Children were the largest age group diagnosed with scabies, at 38%. Males (54%) were diagnosed with scabies more than females. The majority of diagnoses were made by visualizing ova, feces, or mites on light microscopy (58%). At the time of diagnosis, 45% of patients had been misdiagnosed by another provider. Topical permethrin was the most common treatment used (69%), followed by a combination of topical permethrin and oral ivermectin (23%), oral ivermectin (7%), and other treatments (1%). Conclusion: Our findings suggest that more accurate and faster diagnostic methods are needed to limit unnecessary treatment and expedite appropriate therapy for scabies.

Dupilumab for atopic dermatitis

In The Lancet, the LIBERTY AD CHRONOS study by Andrew Blauvelt and colleagues of long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids portends a coming revolution in the treatment of atopic dermatitis. Dupilumab seems to be for atopic dermatitis what etanercept was to psoriasis, an effective, safe treatment that might represent a quantum leap forward in our ability to help to improve the lives of patients. For individuals with moderate-to-severe atopic dermatitis, quality of life is greatly affected and can be worse than in patients with psoriasis. For decades, treatment of severe atopic dermatitis has focused on use of topicals and non-specific systemic immunosuppressive agents, often with unsatisfactory results. Dupilumab is a fully human monoclonal antibody that binds to interleukin 4Ra, a component of the interleukin-4 and interleukin-13 receptors, which inhibits their signalling and downregulates type 2 immunity. Dupilumab was granted Breakthrough Therapy status in 2014 on the basis of phase 2 trial results and showed safety and efficacy as a monotherapy for moderate-to-severe atopic dermatitis (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2) over 16 weeks in 2016. US Food and Drug Administration (FDA) approval was obtained in March, 2017. Dupilumab is the first FDA-approved biologic therapy for the treatment of adult patients with moderate-to-severe atopic dermatitis, and its approval has been long-awaited by dermatologists and individuals with atopic dermatitis. A major strength of this CHRONOS study lies in its “real world” design. The randomised, placebocontrolled, double-blind study enrolled 740 patients with atopic dermatitis who had failed to achieve disease control on topical treatment alone and allowed them to stay on their topicals while using dupilumab. 319, 106, and 315 participants were randomly assigned to dupilumab 300 mg weekly plus topical corticosteroids, dupilumab 300 mg every 2 weeks plus topical corticosteroids, and placebo plus topical corticosteroids, respectively. Topical therapies allowed in this study included both corticosteroids and calcineurin inhibitors. Furthermore, patients could come on and off their topical therapies throughout the 52 week study period based on their disease activity. As opposed to many clinical trials in which new agents are tested solely as monotherapy, CHRONOS allowed concomitant use of topical agents along with dupilumab, a major strength of this study as it provides data that are more relevant to real world practice. The findings of this study show dupilumab to be a highly effective treatment for atopic dermatitis compared to placebo; significant improvement across a range of atopic dermatitis disease activity indices is reported—including Investigator’s Global Assessment (IGA) 0/1 and Eczema Area and Severity Index (EASI; p<0·0001, compared with the placebo group). After 1 year of treatment, an IGA 0/1 and 2-point or more improvement in IGA from baseline was seen in 40% (108 of 270) of participants in the 300 mg weekly group and 36% (32 of 89) in the 300 mg every 2 weeks group versus 13% (33 of 264) in the placebo group (p<0·0001, each dose group vs placebo plus topical corticosteroids); EASI-75 was achieved by 64% (173 of 270), 65% (58 of 89), and 22% (57 of 264), respectively (p<0·0001, each dose group vs placebo plus topical corticosteroids). Over the year, the overall rates of adverse events were similar across the treatment groups, and the placebo plus topical corticosteroids group had higher overall rates of serious adverse events and discontinuations due to adverse events. An additional benefit of a year-long study is to assess efficacy of dupilumab in treating atopic dermatitis over a period long enough to detect flares triggered by seasonal changes. Demonstration of safety and efficacy over this longer study period is also crucial Published Online May 4, 2017 http://dx.doi.org/10.1016/ S0140-6736(17)31192-3

A disease of the present: scurvy in "well-nourished" patients.

To the Editor: Scurvy, vitamin C (ascorbic acid) deficiency, is linked historically to sailors and unbalanced diets. Despite current accessibility to foods containing ascorbic acid, we present two recent cases of scurvy in otherwise apparently “well fed” individuals. A 30-year-old man was admitted for anemia (hemoglobin 7.9 g/dL), leg hematoma, and rash. The patient had been healthy, but exclusively ate fast food with almost no intake of fresh fruits or vegetables. He had poor dentition without gingival bleeding and multiple perifollicular papules on the legs with corkscrew hairs (Fig 1). A biopsy of one of the petechial lesions on the leg revealed histologic findings consistent with scurvy (Fig 2). The patients serum vitamin C level was less than 0.12 mg/dL (normal 0.2-1.9 mg/dL). After the patient was prescribed 2000 mg of ascorbic acid daily, his eruption improved. Fig 1 Scurvy. Multiple perifollicular papules and petechiae with corkscrew hairs on the legs of Patient 1. Fig 2 Scurvy. Routinehematoxylin-eosin stain at 10× showing a superficial perivascular and perifollicular lymphohistiocytic infiltrate (black arrows) with numerous perifollicular extravasated red blood cells. Follicular hyperkeratosis (red arrowhead ... A 55-year-old woman with a history of hypothyroidism, hepatic hemangioma, and fatty liver presented with a new leg rash. She had small, nonpruritic, petechial perifollicular macules on bilateral lower extremities. Based on clinical findings and serum vitamin C level less than 0.12 mg/dL, scurvy was diagnosed. After several days of multivitamin supplementation, her eruption improved. Retrospectively, she reported eating only ½ cup or less of fruits and no vegetables daily and consuming 10 to 14 meals per week at common fast food restaurants. She drank several cans of diet soda 3 or more times per day, expressed a dislike for orange juice, and had been taking no multivitamins. Fast food intake has dramatically increased since the 1970s.1 Time constraints, convenience, and lifestyle have increased the contribution of fast food in the American diet,2 accounting for nearly 50% of an average familys food budget.3,4 Fast food intake is associated with a higher intake of fried potato, hamburger, pizza, and soft drinks, and lower intake of fruits, vegetables, and milk.1,2 While many fast food restaurants offer more healthful choices, patrons may not select these items. Despite availability of healthy fast food options in Australian restaurants, a small minority of Australians were purchasing them.5 A cultural change may be needed before Americans choose healthier substitutes over the traditional burger and fries. Even though scurvy had become rare in the developed world, a resurgence of scurvy may be another indication of the larger problem with the American diet, a diet with insufficient intake of fresh foods and with implications for obesity and diabetes.

Ignoring the "Itch": The Global Health Problem of Scabies

Infestation with Sarcoptes scabiei var. hominis is a common human parasitic affliction endemic in tropical developing countries. Scabies is transmitted by close person-person contact, and outbreaks have been reported in reception centers for asylum seekers. Scabies presents clinically as extremely pruritic excoriated papules and linear burrows in the skin. This infestation predisposes to bacterial skin infections that can result in serious complications affecting the kidneys and possibly the heart. Treatment of individuals with scabies and their close contacts involves the use of antiparasitic agents. First-line treatment is topical 5% permethrin cream. Community mass drug administration, followed by active case finding with targeted treatment, is a promising approach that can reduce the prevalence of both scabies and bacterial skin infections. Organizations such as the International Alliance for the Control of Scabies are advocating for the development of integrated disease control strategies in an effort to decrease scabies infestation worldwide.

Folliculocentric Lichen Sclerosus et Atrophicus in a 10-year-old Girl

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory scarring disease with a predilection for the anogenital area; however, 15%-20% of LSA cases are extragenital. The folliculocentric variant is rarely reported and less well understood. The authors report a rare case of extragenital, folliculocentric LSA in a 10-year-old girl. The patient presented to the dermatology clinic for evaluation of an asymptomatic eruption of the arms and legs, with no vaginal or vulvar involvement. Physical examination revealed the presence of numerous 2-4 mm, mostly perifollicular, hypopigmented, slightly atrophic papules and plaques. Many of the lesions had a central keratotic plug. Cutaneous histopathological examination showed features of LSA. Based on clinical and histological findings, folliculocentric extragenital LSA was diagnosed.

Early Congenital Syphilis: Recognising Symptoms of an Increasingly Prevalent Disease:

Background: Congenital syphilis (CS) is an infectious disease resulting from transplacental transmission of Treponema pallidum spirochetes from an infected mother to fetus during pregnancy. While uncommon, CS has shown an increased incidence in Canada and the United States since 2001 and 2012, respectively. Case Report: We present the case of a 5-week-old female infant with blistering rash on the palms and soles. The infant displayed decreased movement of the left upper extremity, clinically consistent with Parrot pseudoparalysis. Cutaneous involvement was limited to few tan crusted papules on the palms and soles. Mother reported a “false-positive” result of rapid plasma reagin (RPR) testing at 31 weeks. Cerebrospinal fluid studies of the infant resulted with positive Venereal Disease Research Laboratory (VRDL) test and positive microhemagglutination assay (MHA-TP). Histopathology of a crusted papule revealed a lichenoid infiltrate composed of lymphocytes, histiocytes, and plasma cells. Immunohistochemical staining for T pallidum was negative. The patient completed treatment with a 10-day course of intravenous penicillin. Discussion: While CS is largely considered a historic entity, it has been increasing in incidence in the United States since 2012 and in Canada since the early 2000s. Diagnosis of CS can be difficult as infants may be asymptomatic or present with nonspecific signs. This case highlights the presentation of minimal cutaneous involvement as well as skeletal involvement after birth. RPR testing may result in false negatives or indeterminate results, further complicating diagnosis. Given these difficulties in screening and the increasing incidence of CS, clinicians may need to refamiliarise themselves with its clinical findings.