David A. Wetter

Incidence of Hidradenitis Suppurativa and Associated Factors: A Population-Based Study of Olmsted County, Minnesota

There are no population-based incidence studies of hidradenitis suppurativa (HS). Using the medical record linkage system of the Rochester Epidemiology Project, we sought to determine the incidence of the disease, as well as other associations and characteristics, among HS patients diagnosed in Olmsted County, Minnesota, between 1968 and 2008. Incidence was estimated using the decennial census data for the county. Logistic regression models were fit to evaluate associations between patient characteristics and disease severity. A total of 268 incident cases were identified, with an overall annual age- and sex-adjusted incidence of 6.0 per 100,000. Age-adjusted incidence was significantly higher in women compared with men (8.2 (95% confidence interval (CI), 7.0-9.3) vs. 3.8 (95% CI, 3.0-4.7). The highest incidence was among young women aged 20-29 years (18.4 per 100,000). The incidence has risen over the past four decades, particularly among women. Women were more likely to have axillary and upper anterior torso involvement, whereas men were more likely to have perineal or perianal disease. In addition, 54.9% (140/255) patients were obese; 70.2% were current or former smokers; 42.9% carried a diagnosis of depression; 36.2% carried a diagnosis of acne; and 6% had pilonidal disease. Smoking and gender were significantly associated with more severe disease.

Incidence of Dermatomyositis and Clinically Amyopathic Dermatomyositis: A Population-Based Study in Olmsted County, Minnesota

OBJECTIVES To identify new and existing cases of dermatomyositis and its subtypes in Olmsted County, Minnesota, from 1976 through 2007, and to establish a population-based estimate of the incidence and prevalence of dermatomyositis and amyopathic dermatomyositis. DESIGN Retrospective population-based study. SETTING Community-based epidemiology project. Patients Patients with a diagnosis of dermatomyositis were identified from the Rochester Epidemiology Project. MAIN OUTCOME MEASURES Incidence of dermatomyositis and clinically amyopathic dermatomyositis and risk of malignancy in clinically amyopathic dermatomyositis. RESULTS Of the 29 patients identified, 6 (21%) had the clinically amyopathic subtype of dermatomyositis and 22 (76%) were female. Overall age- and sex-adjusted incidence of dermatomyositis including all subtypes was 9.63 (95% confidence interval [CI], 6.09-13.17) per 1 million persons and 2.08 (95% CI, 0.39-3.77) per 1 million persons for clinically amyopathic dermatomyositis. Age- and sex-adjusted prevalence for all subtypes of dermatomyositis was 21.42 (95% CI, 13.07-29.77) per 100,000 persons. Eight patients (28%) had a malignant condition during the study period; the risk of malignancy (odds ratio) for classic dermatomyositis compared with clinically amyopathic dermatomyositis was 4.61 but was not statistically significant (95% CI, 0.22-96.09) (P=.44). CONCLUSIONS Dermatomyositis is a rare disease, and clinically amyopathic dermatomyositis represents an estimated 20% of all dermatomyositis cases. Larger population-based studies are needed to estimate the risk of malignancy associated with subtypes of dermatomyositis, particularly clinically amyopathic dermatomyositis.

Lupus-Like Syndrome Attributable to Anti―Tumor Necrosis Factor α Therapy in 14 Patients During an 8-Year Period at Mayo Clinic

OBJECTIVE To examine clinical characteristics, laboratory features, and outcomes of patients with lupus-like syndrome attributable to anti-tumor necrosis factor alpha (TNF-alpha) therapy. PATIENTS AND METHODS We performed a retrospective review of patients with lupus-like syndrome attributable to anti-TNF-alpha therapy at Mayo Clinics site in Rochester, MN, between July 1, 2000, and June 30, 2008. RESULTS Of 14 patients (mean age at disease onset, 46.2 years), 12 (86%) were female. Ten patients (71%) had Crohn disease, and 4 (29%) had rheumatoid arthritis. Thirteen patients (93%) originally were treated with infliximab, and 1 (7%) was treated with adalimumab. A lupus-ike syndrome occurred after a mean treatment duration of 16.2 months. Features of lupus included presence of antinuclear antibodies (14 patients [100%]), arthritis (13 patients [93%]), anti-double-stranded-DNA antibodies (10 patients [71%]), cutaneous findings (malar rash, discoid rash, or photosensitivity, 4 patients [29%]), serositis (4 patients [29%]), hematologic abnormalities (4 patients [29%]), oral ulcers (4 patients [29%]), and lupus anticoagulant (1 patient [7%]). No patient had renal or neurologic abnormalities. All patients improved after stopping anti-TNF-alpha therapy (mean time to improvement, 2.9 months). Four (80%) of 5 patients tolerated an alternative TNF-alpha inhibitor (adalimumab, 3 patients; etanercept, 1 patient) without recurrence of lupus-like syndrome. CONCLUSION Compared with previous studies, cutaneous findings were less frequent and arthritis was more frequent in our cohort of patients. Some patients were able to tolerate an alternative TNF-alpha inhibitor without recurrence of lupus-like syndrome.

Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist

Erythema multiforme (EM) is an uncommon, immune‐mediated disorder that presents with cutaneous or mucosal lesions or both. In herpes simplex virus (HSV)–associated EM, the findings are thought to result from cell‐mediated immune reaction against viral antigen‐positive cells that contain the HSV DNA polymerase gene (pol ). The target lesion, with concentric zones of color change, represents the characteristic cutaneous finding seen in this disorder. Although EM can be induced by various factors, HSV infection continues to be the most common inciting factor. Histopathologic testing and other laboratory investigations may be used to confirm the diagnosis of EM and to differentiate it from other clinical imitators. Imitators of EM include urticaria, Stevens‐Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweets syndrome, Rowells syndrome, polymorphus light eruption, and cutaneous small‐vessel vasculitis. Because disease severity and mucosal involvement differ among patients, treatment should be tailored to each patient, with careful consideration of treatment risk vs benefit. Mild cutaneous involvement of EM can be managed primarily with a goal of achieving symptomatic improvement; however, patients with HSV‐associated recurrent EM and idiopathic recurrent EM require treatment with antiviral prophylaxis. Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance. With this review, we strive to provide guidance to the practicing dermatologist in the evaluation and treatment of a patient with EM.

Calcinosis Cutis Occurring in Association With Autoimmune Connective Tissue Disease: The Mayo Clinic Experience With 78 Patients, 1996-2009

OBJECTIVE To describe characteristics and treatment of patients with calcinosis cutis in the clinical setting of autoimmune connective tissue disease (ACTD). DESIGN Retrospective study. SETTING Tertiary referral center. PATIENTS Seventy-eight patients with calcinosis cutis and ACTD between 1996 and 2009. MAIN OUTCOME MEASURES Clinical features, treatments, and outcomes of patients with calcinosis cutis in the clinical setting of ACTD. RESULTS Of 78 patients (mean age at onset of calcinosis cutis, 40.1 years), 64 (82%) were female. The following diseases were associated with calcinosis cutis: dermatomyositis (n = 30) with classic (n = 15), juvenile (n = 14), and amyopathic (n = 1) subtypes; systemic sclerosis with limited cutaneous scleroderma (n = 24); lupus panniculitis (n = 4); systemic lupus erythematosus (n = 2); mixed connective tissue disease (n = 4); overlap connective tissue disease (n = 6); undifferentiated connective tissue disease (n = 6); polymyositis (n = 1); and rheumatoid arthritis (n = 1). Therapy for calcinosis cutis consisted of medical treatment alone (n = 19), surgical therapy alone (n = 11), combined medical and surgical treatment (n = 17), no treatment (n = 30), and unknown (n = 1). Diltiazem hydrochloride was the most commonly used medical therapy, with 9 of 17 patients having a partial response. Twenty-eight patients had surgical excision of 1 or more lesions of calcinosis cutis: 22 had a complete response, 5 had a partial response, and 1 had no response. CONCLUSIONS Dermatomyositis and systemic sclerosis were the most common ACTDs associated with calcinosis cutis. Although no treatment was uniformly effective, surgical excision of symptomatic lesions and medical treatment with diltiazem provided benefit for some patients.

Vasculitis Associated With Tumor Necrosis Factor-α Inhibitors

OBJECTIVE To describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors. PATIENTS AND METHODS This is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti-TNF-α therapy. RESULTS Of 8 patients with vasculitis associated with anti-TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti-TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation. CONCLUSION Cutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed.

Clinical, Etiologic, and Histopathologic Features of Stevens-Johnson Syndrome During an 8-Year Period at Mayo Clinic

OBJECTIVE To examine clinical, etiologic, and histologic features of Stevens-Johnson syndrome and to identify possible correlates of clinical disease severity related to etiologic and histopathologic findings. PATIENTS AND METHODS This is a retrospective review of patients seen at Mayo Clinic between January 1, 2000, and December 31, 2007. RESULTS Of 27 patients (mean age, 28.1 years), 22 (81%) had involvement of 2 or more mucous membranes, and 19 (70%) had ocular involvement. Medications, most commonly antibiotics and anticonvulsants, were causative in 20 patients. Mycoplasma pneumoniae infection caused 6 of the 27 cases. Corticosteroids were the most common systemic therapy. No patients with mycoplasma-induced Stevens-Johnson syndrome had internal organ involvement or required treatment in the intensive care unit, in contrast to 4 patients each in the drug-induced group. Three patients had chronic ocular sequelae, and 1 died of complications. Biopsy specimens from 13 patients (48%) showed epidermal necrosis (8 patients), basal vacuolar change (10 patients), and subepidermal bullae (10 patients). Biopsy specimens from 11 patients displayed moderate or dense dermal infiltrate. Histologic features in drug-induced cases included individual necrotic keratinocytes, dense dermal infiltrate, red blood cell extravasation, pigment incontinence, parakeratosis, and substantial eosinophils or neutrophils. CONCLUSION Our clinical and etiologic findings corroborate those in previous reports. M pneumoniae-induced Stevens-Johnson syndrome manifested less severely than its drug-induced counterpart. The limited number of biopsies precludes unequivocal demonstration of histopathologic differences between drug-induced and M pneumoniae-induced Stevens-Johnson syndrome.

Effectiveness of Intravenous Immunoglobulin Therapy for Skin Disease Other Than Toxic Epidermal Necrolysis: A Retrospective Review of Mayo Clinic Experience

OBJECTIVE To examine retrospectively the use and effectiveness of intravenous immunoglobulin (IVIg) treatment of various skin diseases, primarily immunobullous disease. PATIENTS AND METHODS We identified patients who had received IVIg therapy for skin disease between 1996 and 2003 at the Mayo Clinic in Rochester, Minn, Scottsdale, Ariz, and Jacksonville, Fla, and retrospectively reviewed their medical records. RESULTS Eighteen patients were treated with IVIg for various skin diseases: immunobullous disease in 11 adults (pemphigus vulgaris [7 patients], bullous pemphigold [3], and cicatricial pemphigoid [1]); dermatomyositis (2); mixed connective tissue disease (1); chronic urticaria (1); scleromyxedema (1); leukocytoclastic vasculitis (1); and linear IgA bullous disease (1). Responses of patients by type of disease were as follows: pemphigus vulgaris, 1 partial response (PR) and 6 no response (NR); bullous pemphigoid, 1 complete response (CR) and 2 NR; cicatricial pemphigoid, 1 NR; dermatomyositis, 1 CR and 1 PR; mixed connective tissue disease, 1 CR; chronic urticaria, 1 CR; scleromyxedema, 1 CR; leukocytoclastic vasculitis, 1 PR; and linear IgA bullous disease, 1 CR. Six patients (33%) experienced CR, 3 (17%) had PR, and 9 (50%) had NR to IVIg therapy. All 9 nonresponders were adult patients with immunobullous disease. CONCLUSION Although this was a retrospective study of a small cohort of a mixture of patients, the findings emphasize that our experience with IVIg treatment for skin disease, particularly immunobullous disease, is less favorable than that reported previously. Further studies are needed to verify the efficacy of IVIg for skin disease.

Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: The Mayo Clinic experience, 1998 to 2010

BACKGROUND Tumor necrosis factor (TNF)-α antagonists have been associated with the induction of de novo or worsening psoriasis. OBJECTIVE We sought to retrospectively examine the clinical characteristics and outcomes of patients with psoriasis associated with anti-TNF-α therapy. METHODS We performed a retrospective review of patients with new-onset or worsening psoriasis during TNF-α inhibitor therapy between 1998 and 2010. RESULTS Of the 56 patients (mean age at psoriasis onset, 48.1 years), 41 (73%) were female. In all, 22 patients (39%) had Crohns disease and 14 (25%) had rheumatoid arthritis. Thirty patients (54%) were treated with infliximab, 19 (34%) with adalimumab, and 7 (12%) with etanercept. New-onset or worsening psoriasis occurred after a mean treatment duration of 17.1 months. Plaque psoriasis (n = 27), palmoplantar pustulosis (n = 25), scalp psoriasis (n = 12), generalized pustular psoriasis (n = 7), erythrodermic psoriasis (n = 2), and inverse psoriasis (n = 2) were the cutaneous presentations. Among the 39 patients for whom full treatment response data were available, 33 (85%) had a complete or partial response; combined response rates (complete and partial) were slightly higher among those who discontinued anti-TNF-α therapy (16 of 17 patients [94%]) than among those who continued anti-TNF-α therapy (17 of 22 patients [77%]). LIMITATIONS Retrospective nature, possible referral bias, and lack of complete follow-up for some patients are limitations. CONCLUSION Although some patients sufficiently controlled their psoriasis while continuing anti-TNF-α therapy, those who discontinued therapy achieved higher rates of complete response. Further studies should explore the efficacy and safety of switching to an alternative anti-TNF-α agent.

Calcinosis cutis in autoimmune connective tissue diseases

Calcinosis cutis is a chronic condition involving insoluble calcified deposits of the skin and subcutaneous tissue. It is commonly associated with autoimmune connective tissue diseases and can be a source of pain and functional disability. The likelihood of developing calcinosis varies among the autoimmune connective tissue diseases, with systemic sclerosis and dermatomyositis being the most commonly associated. Identification of therapy for this challenging disorder has been hampered by a paucity of large controlled trials. Although there is no uniformly effective treatment for calcinosis cutis, several surgical and medical therapies have demonstrated varying degrees of benefit in the treatment of calcinosis, including surgical excision, laser therapy, extracorporeal shock wave lithotripsy, diltiazem, minocycline, colchicine, and topical sodium thiosulfate, along with others. Recommendations for the diagnosis and therapy of calcinosis cutis in patients with autoimmune connective tissue diseases are discussed.