Rokea A. el-Azhary

Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients.

BACKGROUND Erythema elevatum diutinum is a rare condition representing a chronic leukocytoclastic vasculitis. OBJECTIVE Clinical and laboratory features of the disease were reviewed to better understand the disease. METHODS The medical records and histopathologic slides of 13 patients with erythema elevatum diutinum were studied. RESULTS The lesions were violaceous, deep red, or brown and typically were papules or plaques. Lesions were most often located on the extensor surfaces of the extremities. Associated medical problems included hematologic abnormalities in six patients: IgA clonal gammopathies (four), multiple myeloma (one), and myelodysplasia (one). Erythema elevatum diutinum preceded the myeloproliferative disorders by an average of 7.8 years. All patients showed vasculitis. Leukocytoclasia was present in 27 of 35 specimens. The predominant cell type in the inflammatory infiltrate was polymorphonuclear leukocytes or a mixture of polymorphonuclear leukocytes and lymphocytes. CONCLUSION The most significant finding of this study is the association of erythema elevatum diutinum with hematologic disease, most frequently an IgA monoclonal gammopathy.

Relevant contact sensitivities in patients with the diagnosis of oral lichen planus

BACKGROUND The concept of contact allergy aggravating or inducing oral lichenoid mucositis diagnosed as oral lichen planus (OLP) is well recognized but somewhat controversial. OBJECTIVE We sought to identify clinically relevant contact allergens that may be important in the management of patients with OLP. METHODS We retrospectively reviewed patients with OLP who had patch tests performed at Mayo Clinic Rochester and Mayo Clinic Scottsdale from 1994 to 1997 and 1988 to 1997, respectively. RESULTS Patch tests were performed on 46 patients with a clinical and histopathologic diagnosis of OLP. Of these, 25 (54%) had positive patch test results. Eighteen (72%) of the patients with positive results had clinically relevant reactions. Of the patients with positive metal reactions, 5 had improvement after removal of the metal prosthesis or restoration. Six others noted that their most troublesome areas were adjacent to metal dental restorations. Six patients with reactions to flavorings and one patient with an acrylate dental retainer sensitivity had improvement after avoiding these allergens. CONCLUSION Our findings support the concept that contact allergy to metals, flavorings, and plastics can be important in the pathogenesis and management of patients with oral lichenoid mucositis diagnosed as OLP.

Chronic Hepatitis C and Skin Diseases: A Review

OBJECTIVE To emphasize the ongoing role of chronic hepatitis C virus (HCV) infection in the cause or exacerbation of severe dermatologic disorders. DESIGN We present two case reports to outline the pertinent findings in hepatitis C-related cryoglobulinemia, leukocytoclastic vasculitis, and lichen planus and discuss the main disorders associated with chronic HCV infection. RESULTS Chronic HCV infection has recently been recognized in association with various skin disorders. The most commonly reported association is the triad of leukocytoclastic vasculitis, cryoglobulinemia, and chronic HCV infection. Other cutaneous disorders associated with HCV infection include porphyria cutanea tarda, lichen planus, erythema nodosum, urticaria, erythema multiforme, and polyarteritis nodosa. CONCLUSION Patients with onset or exacerbation of these disorders should undergo assessment for HCV infection.

A Comparison of Morphologic Features, Flow Cytometry, TCR-Vβ Analysis, and TCR-PCR in Qualitative and Quantitative Assessment of Peripheral Blood Involvement by Sézary Syndrome

The strengths and weaknesses of various laboratory methods for peripheral blood (PB) Sézary cell quantitation have not been compared rigorously. In this study, manual Sézary cell counting, qualitative and quantitative flow cytometry, T-cell receptor (TCR) Vbeta flow cytometry, and TCR polymerase chain reaction were performed on PB specimens from 11 patients with Sézary syndrome (SS), 9 with reactive erythroderma, 6 with mycosis fungoides, and 11 healthy control subjects. These methods identified neoplastic cells in more than 90% of SS cases. The diagnostic specificities of these tests varied; they were enhanced by applying criteria proposed by the International Society for Cutaneous Lymphoma. Comparison of sequentially analyzed specimens from 6 patients with SS revealed that although the absolute number of clonal cells was reduced, in some cases, these cells still constituted the vast majority of the CD4+ T-cell subset, suggesting that quantitative subset analysis might be sufficient to monitor changes in the PB tumor burden.

Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies

Background  Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (≤ 5 mm in depth).

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.

Clinical, histopathologic, and immunophenotypic features of lymphomatoid papulosis with CD8 predominance in 14 pediatric patients.

BACKGROUND Lymphomatoid papulosis (LyP) is a cyclic papulonodular eruption that is clinically benign and histologically malignant. Association with hematologic neoplasias has been reported in 5% to 20% of all cases. OBJECTIVE We sought to review the clinical and histopathologic features of LyP in pediatric patients. METHODS We searched for the records of all patients with a clinical and histopathologic diagnosis of LyP seen at our clinic from January 1991 through April 2008. The cases of pediatric patients (aged < 20 years) were reviewed in detail. RESULTS Of 123 patients with LyP identified, 14 (11%) were in the pediatric age group. Most were male (64%); mean age of onset was 12 years. Type A LyP was identified in 12 patients, one patient had type B, and none had type C (type not determined in one case). Ten cases showed CD8 predominance by immunohistochemistry. T-cell intracytoplasmic antigen staining was positive in 3 cases of CD8(+) LyP type A and the one case of LyP type B. Lesional T-cell receptor gene rearrangement studies were negative in 9 of 10 patients with LyP type A. The average follow-up time was 5.5 years. Lesions improved with treatment in most cases, and none of the cases were associated with hematologic malignancies. LIMITATIONS This was a retrospective review. CONCLUSIONS Among our pediatric patients, we noted a predominance of CD8(+) LyP, which does not seem to have an aggressive course. Further longitudinal studies are necessary to evaluate prognostic differences between CD4(+) and CD8(+) LyP and their biological significance.

A Morbilliform Variant of Vancomycin-Induced Linear IgA Bullous Dermatosis

BACKGROUND Linear IgA bullous dermatosis is an autoimmune blistering disease characterized clinically by the presence of small tense blisters and immunologically by the presence of IgA at the dermal-epidermal junction. Idiopathic, systemic disease-related, and drug-related versions of this disorder have been described, with the latter most commonly associated with vancomycin. OBSERVATIONS We describe 2 patients with vancomycin-associated linear IgA bullous dermatosis who presented with a morbilliform eruption that lacked blistering. Lesional and perilesional tissue from each patient was examined by light microscopy and direct immunofluorescence. Histopathologic examination findings revealed vacuolar interface dermatitis with a mixed inflammatory infiltrate and occasional eosinophils, consistent with a drug eruption. Direct immunofluorescence revealed IgA deposited in a linear pattern at the dermoepidermal junction. In both patients, the results of indirect immunofluorescence using both IgG and IgA were negative. CONCLUSIONS These cases highlight the existence of a new form of linear IgA bullous dermatosis presenting as a morbilliform drug eruption. Both patients were following extensive medication regimens, including use of multiple antibiotics. The diagnosis of linear IgA bullous dermatosis allowed us to target vancomycin as the likely allergen and begin treatment. In light of these findings, direct immunofluorescence may be a useful diagnostic adjunct in determining the cause of drug eruptions.

Azathioprine: current status and future considerations.

Azathioprine, a mercaptopurine analog of adenine and hypoxanthine, was developed in the 1950s 1 as an antineoplastic agent designed to improve the rate of inactivation of its parent drug, mercaptopurine. It is considered to be the prodrug for mercaptopurine, with an imidazolyl group attached to the SH group of mercaptopurine to protect it from in vivo oxidation (Fig. 1). In tissues, azathioprine is nonenzymatically converted to mercaptopurine. Animal studies have shown that azathioprine has a higher therapeutic index and is a better immunosuppressant than mercaptopurine. 2 Azathioprine is now widely used as an adjunctive immunosuppressive agent in patients receiving solid-organ transplants, and in rheumatology, dermatology, and gastroenterology as an immunosuppressant and a corticosteroid-sparing agent; 3 mercaptopurine is used principally to treat childhood leukemias.

Chronic hepatitis C, cryoglobulinemia, and cutaneous necrotizing vasculitis: Clinical, pathologic, and immunopathologic study of twelve patients

BACKGROUND Several patients with chronic hepatitis C infection and cutaneous vasculitis have been described. OBJECTIVE The objective of this study was to define better the features of necrotizing vasculitis and mixed cryoglobulinemia in patients with hepatitis C infection. METHODS A retrospective review of 611 patients with hepatitis C antibodies was conducted. Patients with clinical and histopathologic findings of cutaneous necrotizing vasculitis were identified. Clinical, histologic, and laboratory data were recorded. RESULTS Twelve patients with necrotizing vasculitis and chronic hepatitis C infection were identified. Palpable purpura was the most common clinical presentation. Onset of skin lesions was usually more than 10 years after infection. The lower extremities were affected in all patients. Cryoglobulinemia of the mixed type II was present in 10 of 11 patients. Liver function tests were evaluated at the time of vasculitis in most of the patients. Rheumatoid factor was elevated in all nine patients tested. Total complement was decreased in seven of nine patients, and C4 was decreased in six of seven patients. CONCLUSION Cutaneous vasculitis associated with cryoglobulinemia and hypocomplementemia is not uncommon in the course of chronic active hepatitis C infection. The triad of necrotizing vasculitis, chronic hepatitis C infection, and cryoglobulinemia occurs late after initial infection with hepatitis C. Antibodies to hepatitis C virus should be determined in a patient with necrotizing vasculitis, especially if liver function tests are elevated.