Olayemi Sokumbi

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.

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 and histopathologic review of Schnitzler syndrome: The Mayo Clinic experience (1972-2011)

BACKGROUND Schnitzler syndrome is a rare multisystem disorder, defined by urticaria and monoclonal gammopathy, that is associated with malignancy. Considered a neutrophilic urticarial dermatosis, previous reports have included patients with leukocytoclastic vasculitis. OBJECTIVE We sought to better define the clinical features, histopathology, and outcomes of Schnitzler syndrome. METHODS We retrospectively reviewed clinical records and cutaneous histopathology of all patients with Schnitzler syndrome seen at our institution from January 1, 1972, through July 31, 2011. RESULTS Of the 20 patients identified, 80% had IgM κ monoclonal gammopathy; others had IgG λ (10%), IgG κ (5%), or IgM κ+λ (5%). Patients had fevers (85%), arthralgias (70%), leukocytosis (70%), increased erythrocyte sedimentation rate (70%), bone pain (50%), lymphadenopathy (40%), and organomegaly (5%); 45% developed a hematologic malignancy. Histopathologic examination (n = 14) showed predominantly neutrophilic perivascular and interstitial inflammation (57%) or predominantly mononuclear cell perivascular inflammation (29%), with eosinophils in 50% of cases. None showed leukocytoclastic vasculitis. LIMITATIONS Our study was limited by its retrospective design. CONCLUSION We added 20 patients to approximately 100 reported cases of Schnitzler syndrome. Neutrophilic urticarial dermatosis was the most common histopathologic pattern, but mononuclear cells were predominant in many cases and the infiltrates often contained eosinophils. A high index of suspicion and careful clinicopathologic correlation are needed to avoid diagnostic delays in this syndrome associated with hematologic malignancy.

Vasculitis associated with rheumatoid arthritis: a case–control study

OBJECTIVE The aim of this study was to determine the clinical correlates and predictors of rheumatoid vasculitis (RV). METHODS A retrospective cohort of patients with RV evaluated at a tertiary referral centre between 1 January 2000 and 1 January 2010 was identified. RV cases were compared in a 1:2 ratio to controls (RA without vasculitis) to identify risk factors for developing RV. RESULTS Eighty-six RV cases (58% women, 88% white) were identified. Histopathological confirmation was available for 58% of patients. Cutaneous vasculitis was the most common presentation, followed by vasculitic neuropathy. The median age at presentation was 63 years and the median duration of RA was 10.8 years. One third were current smokers. The majority were seropositive and had elevated inflammatory markers. Treatment was with a range of immunomodulating agents. At 6 months, 38% of patients achieved complete remission, 52% had partial improvement and 10% noted no clinical improvement. Thirty-six per cent relapsed by 5 years and 26% died. After adjusting for age and disease duration, current smoking at RA diagnosis [odds ratio (OR) 1.98], coexistent peripheral vascular disease (OR 3.98), cerebrovascular disease (OR 6.48), severe RA (OR 2.02) (characterized by radiographic erosions, nodulosis on clinical examination or requirement of joint surgery) and the use of biologics (OR 2.80) were found to increase the odds for developing RV; the use of HCQ (OR 0.54, CI 0.31, 0.94) and low-dose aspirin (OR 0.42, CI 0.21, 0.85) was associated with decreased odds for developing RV. CONCLUSION This largest single-centre series of patients with RV suggests that even in recent years, RV remains a serious complication of RA and is associated with significant mortality.

Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States

Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993–2005.

Bullous dermatitis artefacta.

Bullous artefactual dermatoses are rare and may be induced by various techniques, including chemicals, heat, or electrical current. Proving a factitial etiology and identifying the mechanism of injury may be difficult. We describe the clinical features and histopathology of 2 patients with bullous disease induced by electrical current or heat. Physical examination in both patients demonstrated geometrically shaped tense bullae. Skin biopsies revealed epidermal necrosis overlying a pauci-inflammatory subepidermal cleft, with homogenization of underlying superficial dermal collagen. In 1 of the 2 patients, there was prominent vertical elongation of keratinocyte nuclei and also of cytoplasmic processes. Direct immunofluorescence study of skin plus testing of serum by indirect immunofluorescence and enzyme-linked immunosorbent assay for BP180 and BP230 antibodies revealed no evidence for immunobullous disease in either patient. Vertical elongation of keratinocyte nuclei, often attributed to a polarization effect of electrical current, is characteristic of electrical burn but also may be induced by thermal injury. These 2 patients highlight the importance of histopathology in confirming a diagnosis of bullous dermatitis artefacta.

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness.

Provider-to-provider communication in dermatology and implications of missing clinical information in skin biopsy requisition forms: a systematic review.

Various components of the skin biopsy requisition form (SBRF) may contribute to accurate dermatopathologic interpretation.

Epidemiology of Systemic Lupus Erythematosus and Cutaneous Lupus in a Predominantly White Population in the United States

Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993–2005.

Therapeutic dose monitoring of mycophenolate mofetil in dermatologic diseases.

BACKGROUND Mycophenolate mofetil (MMF) is used for prevention of allograft rejection in transplantation medicine. In dermatology it is used as a corticosteroid-sparing agent. The pharmacokinetics of MMF are known to vary by individual. Therapeutic dose monitoring of mycophenolic acid (MPA), the active metabolite of MMF, is used as a guide in transplantation medicine, but limited data exist on the benefit of measuring MPA levels in the management of dermatologic disease. OBJECTIVE We sought to describe the use of MPA level monitoring in the management of dermatologic disease. METHODS We retrospectively searched for cases of patients who were treated with MMF for a dermatologic condition at our tertiary care center, and who had at least 1 trough level measurement of MPA from January 1, 2003, through November 30, 2009. RESULTS Our search identified 24 patients treated with MMF for autoimmune bullous diseases, connective tissue diseases, erythema multiforme, atopic dermatitis, or pyoderma gangrenosum who had at least 1 MPA trough level measured. The range of MPA levels in patients who responded to therapy was 1.2 to 8 μg/mL at a dose range of 1 to 3.5 g/d of MMF. Four cases were analyzed in detail to highlight the use of therapeutic dose monitoring in the management of dermatologic disease. LIMITATIONS This was a retrospective study. CONCLUSION We recommend monitoring MPA levels only in patients not responding to the standard 2-g/d dosage of MMF. MPA levels can help the dermatologist to increase the dose in patients who have poor absorption or to detect therapeutic noncompliance.