PREDICTORS OF DISEASE VARIABILITY IN PEMPHIGUS
Saha, M., Bhogal, B., Black, M. M., Cooper, D., Vaughan, R. W., & Groves, R. W. (2014). Prognostic factors in pemphigus vulgaris and pemphigus foliaceus. British Journal of Dermatology, 170, 116–122.
Pemphigus vulgaris (PV) and foliaceous (PF) are two major forms of the pemphigus group of auto-immune blistering diseases. Patients with PV have mucosal blistering with or without cutaneous bullae, whereas patients with PF have superficial blistering and crusting in sebaceous areas without mucosal involvement. Both diseases are caused by auto-antibodies to desmogleins, which are critical components of the desmosomal junctions connecting keratinocytes in the epidermis. Disruption of these desmosomes results in epidermal blistering. The pemphigus group of diseases has a chronic course with variable severity. With treatment, patients can achieve remission. Before the use of corticosteroids (and other systemic immunosuppression), PV was typically fatal.
Previous studies have examined epidemiological and genetic variables that may affect prognosis in patients with pemphigus. Ethnic group, gender, age at onset, smoking, time to initial treatment, initial disease severity, presence of autoantibodies, and certain major histocompatibility complex alleles have all been implicated. This study sought to characterize how specific epidemiological, immunological, and genetic characteristics related to disease duration (DD) and disease remission (DR) in a small but well-characterized patient group in London, United Kingdom.
Patients with PV or PF treated between 1975 and 2007 were eligible for study entry if they had typical clinical features, a positive biopsy, and/or direct or indirect immunofluorescence (to diagnose the presence of anti-desmoglein antibodies) taken at baseline. Patients also were required to have banked serum, available clinical history, and 4 years of follow-up data. The study end points were DR, defined as months from diagnosis to first clearing of lesions, and DD, defined as years from diagnosis to complete clinical remission and withdrawal of immunosuppression. The study examined epidemiological factors; immunological parameters, measured by the detection of anti-desmoglein 1 and anti-desmoglein 3 levels using indirect immunofluorescence; and genetic studies of human leukocyte antigen (HLA) class II type.
Ninety-five patients met the study inclusion criteria (79 with PV and 16 with PF). The study found a strong positive correlation between DD and DR. Patients with Indo-Asian ethnicity had a longer DD than White-Europeans. No difference was seen in DR or DD between patients with PF and patients with PV. In patients with PV, high initial indirect immunofluorescence with normal human skin was associated increased DR, and baseline anti-desmoglein 3 antibody levels were associated with DD. No other immunological parameters (including change in antibody titers or ratio of anti-desmoglein 1–3) were found to be associated with DD or DR. Ninety-four percent of the patients with PV and 92% of the patients with PF had HLA-DRB1 alleles *04 and *14 (associated with pemphigus), although there was no association between HLA and DR or DD.
Remark: This large study looking at markers of disease course in patients with PV and PF had several interesting findings. The data showed a positive correlation between time to first DR and DD. Indo-Asian patients had significantly longer DD. Furthermore, there was no correlation found between PF or PV and first remission or DD, suggesting that PF and PV are similar in clinical course. Although the study measured an early end point (DR) as well as a late end point (DD) of disease, the outcome measures did not follow International Pemphigus Committee recommendations. In addition, disease severity, morbidity/mortality, and treatment failure/success were not examined as end points in this study. Several published tools, including the autoimmune bullous skin disorder intensity score, exist as an aggregate measure of PV/PF severity.
INTRALESIONAL TREATMENT OF CALCIPHYLAXIS
Strazzula, L., Nigwekar, S. U., Steele, D., Tsiaras, W., Sise, M., Bis, S., … Kroshinsky, D. (2013). Intralesional sodium thiosulfate for the treatment of calciphylaxis. Journal of the American Medical Association Dermatology, 149(8), 946–949.
Calciphylaxis is a disorder of abnormal calcium deposition in blood vessel walls that results in cutaneous necrosis and painful ulceration. Classically, calciphylaxis, also known as uremic gangrene syndrome or calcific uremic arteriolopathy, has been associated with underlying severe renal disease; however, patients often have diabetes mellitus, are obese, or have poor nutritional status. Disease mortality is high (around 80%) and usually occurs because of the development of gangrene and sepsis. Treatment options include normalization of calcium-phosphate levels, wound care, hyperbaric oxygen, intravenous (iv) sodium thiosulfate, iv palmidronate, and iv tissue plasminogen activator. Because calciphylaxis is a rare disease, treatment regimens are based on case series rather than large clinical trials.
Sodium thiosulfate is an inorganic salt that has historically been used in the treatment of cyanide poisoning. Given parenterally, the drug has significant side effects including metabolic acidosis and sodium overload. The authors of this article hypothesized that localized or intralesional sodium thiosulfate (ILST) may be an effective treatment of calciphylaxis without the adverse effects associated with iv treatment. They report a series of four patients with calciphylaxis successfully treated with ILST.
The patients, aged 65–68 years, all had chronic kidney disease stage II, III, or IV. Three of four were also obese, and one had diabetes mellitus. All had biopsy-proven calciphylaxis (although two of four required a second biopsy to confirm the diagnosis). All patients were treated slightly differently. Patient 1 had four injections of 250-mg ILST every month with collagenase and silver nitrate as wound care. Patient 2 had three injections of 250-mg ILST every 2 weeks with collagenase and fenestrated silicone as wound care. Patient 3 had 16 injections of 250- to 750-mg ILST every 1–2 weeks with hydrocolloid dressings as well as systemic treatment with a phosphate binder and calcimimetic. Patient 4 had three consecutive daily treatments with 500-mg ILST as well as iv sodium thiosulfate, a phosphate binder, sildenafil, and pentoxifylline. All patients showed complete healing of their ulcers between 4 and 6 months after the initiation of treatment, and none had metabolic derangements because of treatment.
Remark: Although ILST represents a promising treatment alternative in calciphylaxis, better-controlled studies are needed to provide proof of tolerability and efficacy. These would be challenging trials to perform because calciphylaxis is a rare entity, and each patient and each wound has unique characteristics; however, treatment frequency, dosage, and wound care protocols need to be more uniform before cases can be directly compared. ILST may be challenging to use in many centers because even the iv drug is difficult and expensive to acquire. In addition, calciphylaxis is an exquisitely painful condition, and intralesional injections would likely cause significant patient discomfort. Overall, however, ILST was well tolerated (other than transient pain), and there were no metabolic derangements found because of intralesional injections.
AN OVERVIEW OF SWEET’S SYNDROME
Rochet, N. M., Chavan, R. N., Cappel, M. A., Wada, D. A., & Gibson, L. E. (2013). Sweet syndrome: Clinical presentation, associations, and response to treatment in 77 patients. Journal of the American Academy of Dermatology, 69(4), 557–564.
Sweet’s syndrome presents with “juicy” or edematous red-purple plaques that favor the head and upper extremities. Sweet’s syndrome, also known as febrile neutrophilic dermatosis, has three forms: classic, malignancy associated, and drug related. Classic Sweet’s syndrome has been associated with infections, pregnancy/hormone use, and autoimmune connective tissue diseases. Associated malignancies are frequently hematological, but solid tumors are also seen. To have a diagnosis of Sweet’s syndrome, patients must have both major criteria—typical lesions and confirmatory histopathology—and two of four minor criteria: a known disease association or drug cause, fever, specific hematological parameters, and response to systemic corticosteroid therapy.
The aim of this article was to report on patient characteristics, treatment, and outcomes of a large series of patients with Sweet’s syndrome seen at the Mayo Clinic (Rochester, Minnesota, USA). Patients with a diagnosis of Sweet’s syndrome seen at the clinic between 1992 and 2010 were identified (N = 113), and 36 were excluded based on lack of histopathological or clinical criteria. The researchers evaluated patient demographics, lesion morphology, medical history, histopathology, laboratory data, treatment, and treatment response.
Seventy-seven patients met the criteria for Sweet’s syndrome, and 56% were men. The mean age overall was 57 years; however, patients with malignancy-associated Sweet’s syndrome were significantly older (mean age = 68 years). Lesions most commonly presented on the upper extremities and were typically plaques, papules, or nodules but could also be vesicular or pustular. Twenty-three percent of patients had a preceding infection (most of these were upper respiratory tract infections), 35% had an associated malignancy, and 12% were identified as having a drug-related cause. Of the malignancies, 78% were hematological malignancies, myeloproliferative or myeloplastic syndrome. Both men and women with malignancy-associated Sweet’s syndrome had significantly lower mean hemoglobin levels than patients with classic or drug-associated Sweet’s. Only 39% of patients reported an associated fever, and 16% had a documented associated fever. Patients were most frequently treated with systemic corticosteroids, and the second most common treatment was dapsone. Eighty-two percent of the patients had complete response, and one patient had no response.
Remark: This represents one of the larger case series of patients with Sweet’s syndrome. It both confirms and adds important information to the literature on the subject. The study shows that patients with malignancy-associated Sweet’s syndrome are significantly older and have significantly lower mean hemoglobin values than those with either classic or drug-related Sweet’s syndrome. The authors reinforce the need for healthcare providers to remain aware of the potential paraneoplastic nature of Sweet’s syndrome and to perform an appropriate work-up, especially in patients with these clinical clues. This study was limited by its retrospective and single-center recruitment design. This may account for the deviation of the gender distribution from the traditionally taught 3:1 women-to-men ratio in classic Sweet’s syndrome (and 1:1 ratio in malignancy-associated Sweet’s syndrome). Interestingly, only 39% of patients reported an associated fever, despite fever being part of the “classic” findings and a minor criterion. Overall, however, the study confirmed many of the known disease associations with Sweet’s syndrome and showed that patients typically have complete response to standard management.
Copyright © 2014 by the Dermatology Nurses' Association.