Aileen Y. Chang

Response to Antimalarial Agents in Cutaneous Lupus Erythematosus: A Prospective Analysis

OBJECTIVE To demonstrate response to antimalarial agents in patients with cutaneous lupus erythematosus (CLE) using activity scores from the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a validated outcome measure. DESIGN Prospective, longitudinal cohort study. SETTING University cutaneous autoimmune disease clinic. PARTICIPANTS A total of 128 patients with CLE who presented from January 2007 to July 2010 and had at least 2 visits with activity scores. INTERVENTION Administration of antimalarial agents. MAIN OUTCOME MEASURES Response was defined by a 4-point or 20% decrease in activity score. Response to initiation was determined by the difference between the scores before treatment and at the first visit at least 2 months after treatment. Response to continuation was determined by the difference between the scores at the first visit and the most recent visit while undergoing treatment. RESULTS Of 11 patients who initiated treatment with hydroxychloroquine, 55% were responders (n = 6), showing a decrease in median (interquartile range [IQR]) activity score from 8.0 (3.5-13.0) to 3.0 (1.8-7.3) (P = .03). Of 15 patients for whom hydroxychloroquine failed, 67% were responders to initiation of hydroxychloroquine-quinacrine therapy (n = 10), showing a decrease in median (IQR) activity score from 6.0 (4.8-8.3) to 3.0 (0.75-5.0) (P = .004). Nine of 21 patients who continued hydroxychloroquine treatment (43%), and 9 of 21 patients who continued hydroxychloroquine-quinacrine (43%) were responders, showing a decrease in median (IQR) activity score from 6.0 (1.5-9.5) to 1.0 (0.0-4.5) (P = .01) and 8.5 (4.25-17.5) to 5.0 (0.5-11.5) (P = .01), respectively. CONCLUSIONS The use of quinacrine with hydroxychloroquine is associated with response in patients for whom hydroxychloroquine monotherapy fails. Further reduction in disease activity can be associated with continuation of treatment with antimalarial agents.

Treatment of cutaneous lupus.

Cutaneous lupus erythematosus (CLE) is an autoimmune inflammatory skin disease seen in patients with or without systemic lupus erythematosus. The management of CLE includes treatment and prevention of lesions as well as routine assessment for systemic disease. Treatment options include topical and systemic therapies. Topical therapies include corticosteroids and calcineurin inhibitors. Systemic therapies generally fall under one of three categories: antimalarials, immunomodulators (eg, dapsone and thalidomide), and immunosuppressives (eg, methotrexate and mycophenolate). Evidence for the treatment of CLE has been limited by few prospective studies and the lack of a validated outcome measure (until recently). There is good evidence to support the use of topical steroids and calcineurin inhibitors, although most of these trials have not used placebo or vehicle controls. There have been no randomized, placebo-controlled trials evaluating systemic therapies in the treatment of CLE.

Characterization of clinical photosensitivity in cutaneous lupus erythematosus

BACKGROUND Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. OBJECTIVE We sought to characterize self-reported PS in cutaneous LE (CLE). METHODS The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. RESULTS In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). LIMITATIONS PS was inferred from patient report and not directly observed. CONCLUSIONS Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.

Quality of Life Differences Between Responders and Nonresponders in the Treatment of Cutaneous Lupus Erythematosus

Patients with cutaneous lupus erythematosus (CLE) have very poor quality of life1. When compared to those with other skin diseases, CLE patients are among those most severely affected by their condition. The psychologic aspects of quality of life in CLE are similar to, or worse than, what is experienced by patients with chronic hypertension, congestive heart failure, type 2 diabetes mellitus, and recent myocardial infarction. In considering this, we were interested in assessing whether patients who demonstrated response to treatment also experienced change to their quality of life.

Management Considerations in Extraocular Sebaceous Carcinoma.

BACKGROUND Extraocular sebaceous carcinoma (SC) is a rare malignancy with metastatic potential. The authors present a case of a rapidly growing extraocular SC with equivocal radiographic imaging to highlight challenges in tumor management. OBJECTIVE To examine the existing literature for evaluation and management recommendations of extraocular SC. METHODS AND MATERIALS A comprehensive review of relevant English articles in PubMed through May 2015. RESULTS Tumor-specific staging system and management guidelines do not currently exist for extraocular SC. Mohs micrographic surgery or wide local excision are the most commonly used surgical treatments. Regional/distant metastasis occurs infrequently, but systemic workup with radiographic imaging or sentinel lymph node biopsy may be warranted in select cases. Adjuvant radiation therapy can be considered for recurrent and metastatic tumors. CONCLUSION Extraocular SCs present unique challenges that may benefit from multidisciplinary management. Surgical removal with negative pathologic margins is the mainstay treatment of extraocular SC. Additional studies will help clarify the optimal diagnostic workup and adjuvant treatment of patients.

Providing dermatological care in resource‐limited settings: barriers and potential solutions

Worldwide, skin conditions are the fourth leading cause of nonfatal disease burden and contribute to disability in all age groups. Resource-limited settings (RLS) are characterized by limited access to healthcare providers, fewer healthcare professionals, less developed infrastructure, and reduced availability of medications, supplies and equipment. This article identifies barriers to providing dermatological care in RLS, focusing on lowand middle-income countries (LMICs) and proposes potential solutions to address these barriers. Firstly, dermatologists in RLS are few in number and generally work in urban areas, rarely travelling to rural communities. Patients living outside of urban areas often have difficulty seeing a specialist because of transportation costs, expensive services and concerns about lost income. Teledermatology can help bridge the access gap by mitigating patients’ cost and time concerns. With appropriate infrastructure and support, teledermatology can be implemented within an LMIC health system using in-country teledermatologists, who are familiar with endemic diseases and local healthcare delivery. Establishing outreach clinics is another way in which dermatologists can improve access in RLS. In Botswana, outreach clinics are led by a dermatologist based out of the capital city and rotate weekly among four rural towns. In rural Ethiopia, a mobile dermatology clinic is held twice monthly in two villages and includes a nurse, two community health workers and a dermatologist, who conducts training with local health-centre staff. Secondly, healthcare professionals do not have sufficient dermatology training. Dermatologists can play a crucial role in training healthcare professionals in LMICs, where task shifting is common due to constrained human health resources. Community-based programmes that combine training of primarycare providers with teaching clinics have been successful in Mexico and Patagonia, Argentina, with the latter also including sun protection workshops for children. Diploma programmes exist at the Preah Kossamak Hospital in Cambodia and the Regional Dermatology Training Center in Tanzania. In addition to increased dermatology training of frontline providers, there is ongoing need for dermatology residency and postgraduate programmes in sub-Saharan Africa that train dermatologists with curriculum standards that are modelled after high-income countries but adapted to focus on endemic conditions, locally available resources and local healthcare systems. Such programmes exist through a partnership between Addis Ababa University and the African Leprosy/Tuberculosis Education and Research Center in Ethiopia, the Regional Dermatology Training Center in Tanzania, Mbarara University of Science and Technology in Uganda, and several institutions in South Africa and Nigeria. Thirdly, dermatopathology capacity is poor. In LMICs, allocation of limited pathology resources to dermatopathology is influenced by the perceived utility of histopathology in the management of skin diseases, which in turn is determined by the ability to sample a representative specimen, proper tissue processing and reliable reports. Each of these aspects represents a potential barrier. Biopsy supplies may be initially supported by grants or philanthropy, but ideally they would be sustained by the healthcare facility, which necessitates support from facility leadership and familiarity with customs regulations. Next, availability of histopathology services is often limited. When available, the quality of tissue processing and staining may be suboptimal, and the linkage of results to other aspects of patient care is haphazard. While special stains, immunohistochemistry, and immunofluorescence are not readily available, a study from Kenya and Tanzania concluded that a proper histopathological diagnosis could be rendered after haematoxylin and eosin staining alone in almost 90% of 386 specimens, suggesting that limited resources should not prevent the development of dermatopathology capacity. Point-ofcare polymerase chain reaction techniques to diagnose skin diseases with infectious aetiology will improve timely diagnoses if reliability and affordability can be achieved. Where local dermatopathology is unavailable, store-and-forward teledermatopathology, real-time robotic teledermatopathology and virtual slide systems can be utilized, although implementation of the latter two options is dependent on telecommunication and technology infrastructure. Finally, fundamental dermatological therapies are often not readily accessible in LMICs. Forming a relationship with local pharmacists enables effective advocacy for medications. In western Kenya, a revolving fund pharmacy model allows for steady provision of medications by using revenues generated from sales to restock medications. Furthermore, compounding of essential medicines locally may increase their availability and affordability, although obtaining a consistent supply of raw materials can be a challenge. Additionally, natural sunlight can be used in lieu of phototherapy, although this manner of skin exposure may not always be culturally appropriate. Philanthropy plays an important role, but sustainability is not guaranteed. Importantly, providers in RLS should understand the feasible treatment options for patients, with careful consideration of cost, availability and ability to follow up.

What can the tongue tell you about Sjögren's syndrome?

In Western medicine, examination of the tongue sometimes provides early clues (e.g., erythema, loss of glistening, fissures) to the diagnosis of Sjögren’s syndrome (SS). However, tongue examination is not mentioned or required in the AmericanEuropean Consensus Group criteria. In a patient with stomatopyrosis or glossodynia (tongue or mouth burning), a beefy red tongue with multiple fissures and loss of filiform papillae usually suggests chronic erythematous candidiasis (Fig. A). Erythematous candidiasis is the most common soft-tissue oral lesion in SS patients. Figure B shows a normal tongue. On the other hand, in Traditional Chinese medicine (TCM), examination of the tongue has even greater importance and plays a central role in diagnosis. The tongue is viewed as an important window into the body. The characteristics of the tongue (e.g., color of the tongue body, tongue coating, presence of fissures) are considered a reflection of the body’s internal condition.3 Tongue findings, in connection with other diagnostic tools, are used to diagnose the patient with a TCM pattern. For the TCM physician, correct diagnosis is important, because each TCM pattern is treated with a different combination of Chinese herbs. In understanding TCM, it is important to define the basic terms unique to TCM. Qi is an invisible substance that moves throughout the body and maintains the function of internal organs. Deficiency in qi leads to illness. Yin and yang represent 2 dynamic forces in nature, which interact with each other to create balance. Each organ has both yin and yang, which must be in balance for the organ to function properly. Because of the interdependence of yin and yang, deficiency of one can lead to relative excess of the other and eventually deficiency of the other. TCM also describes 6 external pathogens that can cause disease: wind, cold, summer heat, dampness, dryness, and fire. Furthermore, TCM distinguishes pattern from disease. Pattern is a diagnostic concept that provides details on the condition of a disease at its current stage. Disease is a more general diagnostic concept. Depending on the stage of the disease, a patient may have a particular pattern, so it is possible to have different patterns in the same disease. Conversely, different diseases may have similar patterns. Also, note that TCM patterns do not necessarily correlate clinically to pathologic conditions in Western medicine. Multiple TCM patterns are associated with patients given a diagnosis of SS in Western medicine. In TCM, yin deficiency is often involved in SS. Yin deficiency can be further classified according to signs and symptoms. The spectrum of TCM patterns for SS includes spleen-qi deficiency, spleen-yin deficiency, liver-yin deficiency, kidney-yin deficiency, dry-heat impairing the lung, and blood stasis.4 Table 1 provides further detail on several of these patterns. In a recent pilot study, which compared medical practices and clinical findings in Chinese and American SS patients, both groups exhibited similar tongue findings on physical examination performed by inspection.5 Most patients in both groups had a red tongue with a yellow coating or red tongue with thin coating; some had fissures as well (Figs. C and D). A minority of patients had a purple tongue (Fig. E). These tongue findings provide a significant amount of information for the TCM physician. A red tongue with yellow coating could reflect an abundance of inner heat, and a red tongue with thin coating could reflect the yin deficiency condition of the liver and kidney. A

Scabies—An Ancient Disease With Unanswered Questions in Modern Times

Scabies, believed to have been first described by Aristotle (384-322 bc) in ancient Greece, has been with humankind throughout the ages. During the past decade, there has been a resurgence of global interest in scabies owing to enhanced awareness of its detrimental effect on health. The World Health Organization recently added scabies to its list of neglected tropical diseases (NTDs), which are a group of diseases, primarily infectious, prevalent in tropical and subtropical world regions that cause enduring disfigurement and debilitation, leading to social stigma and the inability to work or attend school. The World Health Organization estimates that more than 1 billion people—about one-sixth of the world’s population—have 1 or more NTDs, which cost developing economies billions of dollars annually. With an NTD designation, the World Health Organization increases the spotlight on Sarcoptes scabiei and calls on organizations, governments, researchers, funders, and policymakers to respond. Why such attention on this mite that does not even burrow beyond the stratum corneum?

Randomized controlled trial to evaluate locally sourced two-component compression bandages for HIV-associated Kaposi sarcoma leg lymphedema in western Kenya: The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study protocol

Background HIV-associated Kaposi sarcoma (KS), among the most frequent cancers seen in sub-Saharan Africa, is associated with a high prevalence of lymphedema. Lymphedema causes progressive functional impairment marked by swelling, physical discomfort, disfiguring changes, skin hardening from fibrosis, poor wound healing, and recurrent skin infection. While compression therapy is considered a major component of lymphedema management, this intervention has never been evaluated in HIV-associated KS lymphedema. Methods/design The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study is a randomized, controlled trial. Due to variable lymphedema stage, we will use block randomization with a 1:1 allocation to assign participants to one of two groups: “Immediate compression” or “Delayed compression.” Those randomized to “Immediate compression” intervention arm will receive weekly two-component compression bandages while receiving chemotherapy, whereas those in the “Delayed compression” control arm will be followed during chemotherapy and then receive compression after chemotherapy is completed. The primary outcome is change in Lower Extremity Lymphedema Index from enrollment at Week 0 to blinded outcome assessment at Week 14 between intervention and control arms. Secondary outcomes are change in leg lymphedema-specific quality of life (LYMQOL) and change in overall health quality of life in cancer (EORTC QLQ C30). Discussion This represents the first study in sub-Saharan Africa to assess a lymphedema-directed intervention for KS, and the intervention—locally sourced two-component compression bandages—is affordable and available. Thus, the KICKS study is an important step towards developing an evidence-based path for regionally relevant management of HIV-associated KS lymphedema. Trial registration This trial was registered at ClinicalTrials.gov on January 19, 2018: identifier NCT03404297.

Response to “Providing dermatological care in resource‐limited settings: barriers and potential solutions” – reply from authors

1 Chang AY, Kiprono SK, Maurer TA. Providing dermatological care in resource-limited settings: barriers and potential solutions. Br J Dermatol 2017; 177:247–8. 2 Mah e A, Hay R. Epidemiology and management of common skin diseases in children in developing countries. Available at: http:// www.who.int/maternal_child_adolescent/documents/fch_cah_05_ 12/en (last accessed 24 December 2017). 3 Mah e A, Faye O, Thiam N’Diaye H et al. Definition of an algorithm for the management of common skin diseases at primary health care level in sub-Saharan Africa. Trans R Soc Trop Med 2005; 99:39–47. 4 Mah e A, Faye O, Thiam N’Diaye H et al. Integration of basic dermatological care into primary health care services in Mali. Bull World Health Organ 2005; 83:935–41. 5 Faye O, Dicko A, Ciss e L et al. D epistage d’un cas de l epre l epromateuse par un agent de sant e p eriph erique: impact du projet TELEDERMALI? Available at: https://www.leprosy-information.org/files/ BALLF%20no%2032.%20juin%202017_0.pdf (last accessed 24 December 2017).