THE NATURAL HISTORY OF PEDIATRIC-ONSET DISCOID LUPUS ERYTHEMATOSUS
Arkin, L. M., Ansell, L., Rademaker, A., Curran, M. L., Miller, M. L., Wagner, A., [horizontal ellipsis] Paller, A. S. (2015). The natural history of pediatric-onset discoid lupus erythematosus. Journal of the American Academy of Dermatology,72(4), 628-633.
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect multiple organ systems including the skin, joints, kidneys, lungs, and nervous system. Approximately 20% of SLE cases present during the first 2 decades of life. Although SLE in children is fundamentally the same disease as in adults, there are several important differences between adult and pediatric SLE. Specifically, pediatric SLE tends to be more severe than adult SLE, with a more aggressive clinical course and increased mortality. In addition, there is a higher frequency of end-organ involvement at onset in children with lupus than in adults, with renal, neurologic, cardiac, and pulmonary involvement seen more commonly at the time of diagnosis. The prognosis of pediatric SLE is tied closely to disease severity at presentation; delays in diagnosis often lead to increased morbidity and mortality.
There are several specific subtypes of cutaneous lupus erythematosus (CLE), including acute CLE, characterized by the localized malar butterfly rash or generalized photosensitive rash; subacute CLE, characterized by an annular rash or papulosquamous (psoriasiform) rash; and chronic CLE, characterized by a wide variety of skin lesions. Discoid lupus erythematosus (DLE) is the most common type of chronic CLE and presents clinically as a sharply demarcated, round, erythematous plaque with a well-formed adherent "carpet-tack" scale; when the scale is removed, follicular plugging is revealed. DLE lesions resolve with scarring.
In the adult population, the frequency of progression of DLE to SLE is reported to range from 0% to 28%, with an interval between onset of DLE and progression to SLE ranging from months to decades. The risk of progression to SLE in children with DLE, however, remains poorly understood.
The objectives of this study were to better understand the natural history of pediatric DLE and to determine the risk of progression of pediatric DLE to SLE. The study design was a retrospective review. The charts of all patients given the diagnosis of DLE before the age of 16 years and seen between 1995 and 2012 by faculty in rheumatology and/or dermatology at the Ann and Robert H. Lurie Children's Hospital in Chicago, IL, were reviewed. At least two health encounters were required. Patients with other manifestations of CLE including acute CLE, subacute CLE, neonatal lupus, tumid lupus, and lupus panniculitis were excluded. DLE lesions were diagnosed based on clinical features or histopathologic confirmation. A patient was considered to have progressed to SLE if four or more of the 1982 SLE American College of Rheumatology criteria were met. Demographic information and clinical data relating to disease characteristics were collected for all patients. Patients were subsequently stratified into four subgroups: (a) DLE with concurrent diagnosis of SLE, (b) DLE with progression to SLE, (c) SLE with laboratory abnormalities but not satisfying 1982 American College of Rheumatology criteria for SLE, and (d) DLE with skin-limited disease through follow-up.
Forty patients aged 16 years or younger at diagnosis of DLE were included in the study. Six patients (15%) were concurrently given the diagnosis of SLE (Group 1). Of the 34 remaining, nine (26%) eventually met criteria for SLE (Group 2). Fifteen (44%) developed laboratory abnormalities without meeting SLE criteria (Group 3), and 10 patients (29%) maintained skin-limited DLE (Group 4) over 5 years of median follow-up (Group 4).
Patients were at greatest risk of SLE progression within the first year after diagnosis. Most patients who developed SLE during the study period had laboratory abnormalities and isolated mucocutaneous disease (discoid lesions, malar rash, oral and nasal ulcers, photosensitivity) but no end-organ damage.
REMARK: The results of this study indicate that pediatric DLE carries a significant risk of progression to SLE. Approximately 40% of patients with DLE in this study developed SLE. Most patients who progressed to SLE, however, met diagnostic criteria with mucocutaneous disease and laboratory testing without developing end-organ damage over 5 years of median follow-up. This suggests that pediatric patients with DLE who develop SLE may have mild systemic disease. The study was limited by the retrospective nature of data collection. The authors note that the greatest limitation, however, may be the average of 5 years of follow-up duration, as several recent adult studies have documented that progression to SLE may take 8-10 years after initial diagnosis to manifest. Given the limited follow-up time, this study may have failed to capture adolescent patients with DLE who progressed to SLE many years after their initial diagnosis. Further long-term prospective studies of DLE are necessary to validate the results of this study and fully understand the natural history of this disease in children. Ultimately, children with DLE require careful long-term monitoring for progression to SLE.
SOCIOECONOMIC AND LIFESTYLE FACTORS AND MELANOMA: A SYSTEMATIC REVIEW
Jiang, A. J., Rambhatla, P. V., &s Eide, M. J. (2015). Socioeconomic and lifestyle factors and melanoma: A systematic review. British Journal of Dermatology, 172, 885-915.
Melanoma is a significant societal health problem. It currently ranks as the fifth most common malignancy in men in the United States and the sixth in women in terms of incidence. There is, therefore, an urgent need to better understand the multiple risk factors that lead to the development of melanoma. Over the years, numerous studies have shown a higher incidence of melanoma and decreased mortality among high-socioeconomic-status (SES) individuals. However, this association is poorly understood.
The objective of this systematic review was to evaluate the existing literature on the association between SES and melanoma incidence and mortality to better assist care providers in understanding social determinants of melanoma epidemiology.
A literature search was conducted by the review authors. Studies were eligible for inclusion if they formally evaluated melanoma screening, incidence, prognosis, and future direction for cancer prevention. Search results were limited to articles in English and conducted as original research. All studies were independently reviewed by all three authors. Each study was assessed for the quality of evidence.
In total, 280 studies met the inclusion criteria and were included in the review. In terms of evidence quality, 24 studies received Grade A, and 256 studies received Grade B.
The results of the review affirm that high SES is, indeed, associated with increased risk of melanoma whereas low SES is associated with increased mortality from melanoma. In general, exposure to agricultural and manufacturing chemicals was associated with increased risk of melanoma. Other lifestyle risk factors included obesity, recreational sun exposure, and use of tanning beds. Unmarried and widowed statuses were also found to be associated with late-stage disease and increased risk of death from melanoma.
REMARK: This review helps to characterize the complex relationship between social determinants and melanoma incidence and mortality. It indicates that, whereas higher SES populations are more likely to be diagnosed with melanoma, lower SES populations have a worse prognosis. It has been hypothesized that this association stems from more vigilance among high-SES populations to consult dermatologists. The study is limited by the fact that it included only English-language studies; important research published in other languages may have therefore been omitted. In addition, the literature search terms related strictly to SES and lifestyle, which may not be completely inclusive. Understanding the lifestyle factors that impact melanoma outcomes may provide an opportunity for more effective targeted interventions, outreach, and education and, ultimately, improve the lives of patients affected by melanoma.
TREATMENT OF ALOPECIA AREATA WITH SIMVASTATIN/EZETIMIBE
Lattouf, C., Jimenez, J. J., Tosti, A., Miteva, M., Wikramanayake, T. C., Kittles, C., [horizontal ellipsis] Schachner, L. A. (2015). Treatment of alopecia areata with simvastatin/ezetimibe. Journal of the American Academy of Dermatology,72(2), 359-361.
Alopecia areata (AA) is a nonscarring immune-mediated hair loss that typically leads to bald patches on the scalp. Clinical manifestation varies from patchy involvement, to diffuse hair thinning, to a more extensive complete loss of scalp hair (generalized AA) or involvement of facial and body hair as well (alopecia universalis).
Several different treatment options have been used with some success, from topicals (steroids, imiquimod, minoxidil), to intralesional injection of steroids, to systemic drugs (steroids, immunomodulatories) for more generalized types. Treatment response is unpredictable and also difficult to gauge, as AA has a 50% chance to self-resolve in 1year. Because of low success rates and many undesirable side effects of systemic drugs used in AA, other treatment options are still being explored.
The objective of the study was to determine the effectiveness of simvastatin/ezetimibe in treating AA. Simvastatin/ezetimibe is a combination of drugs used primarily to treat dyslipidemia. These drugs have been found to have anti-inflammatory and immunomodulatory effects in atherosclerosis.
The study was a prospective pilot study with 29 enrolled subjects. Inclusion criteria are detailed as follows: 18 years old, with 40%-70% of scalp involvement using the North American Hair Research Society scale. The patients had not received systemic treatment for 3 months or topical treatment for 2 weeks. Patients were given only simvastatin/ezetimibe 40 mg/10 mg daily for 24 weeks. Patients who showed 20% regrowth at the 24th week were considered positive responders and were further subdivided to Group A, who continued treatment for an additional 24 weeks, and Group B, who stopped treatment but continued to be monitored.
Results showed that, of the 19 subjects who completed the study, 14 responded to the treatment. Of the patients in Group A, five of seven continued to have hair growth or were stable.
REMARK: Combination of simvastain and ezetimibe is a promising treatment option for patients with AA, especially those requiring systemic treatment because of more extensive involvement. This study is limited by the small number of subjects, high number of dropout/loss to follow-up, and no control group. However, it does open a new arena of treatment to be studied in a more controlled and randomized fashion.