Warren W. Piette

Acute neutrophilic dermatosis with myeloblastic infiltrate in a leukemia patient receiving all-trans-retinoic acid therapy.

We report a case of leukemia-associated acute febrile neutrophilic dermatosis (Sweets syndrome) that is unique because its initial histologic findings mimicked leukemia cutis. Otherwise, the clinical manifestations and response to corticosteroid therapy were typical of Sweets syndrome. The onset of the dermatosis coincided with the onset of neutrophilic differentiation induced by single-agent leukemia therapy with all-trans-retinoic acid (ATRA). Subsequent exacerbation of the manifestations of Sweets syndrome and the ultimate conversion of the histologic picture to the expected mature neutrophilic dermal infiltrate coincided with the completion of neutrophilic differentiation in the peripheral blood and bone marrow. The ability of immature neutrophil precursors to induce cutaneous lesions of Sweets syndrome may indicate an ATRA-induced functional maturation that slightly precedes its effect on morphologic maturation. We conclude that a cutaneous infiltrate of early neutrophil precursors does not preclude a diagnosis of Sweets syndrome in patients with acute leukemia who respond to ATRA therapy.

Cutaneous Manifestations of Antiphospholipid Antibody Syndrome

Many different cutaneous lesions or cutaneous-systemic syndromes can be the presenting sign of antiphospholipid antibody syndrome (APS), or can develop during the course of disease. None of these conditions are specific for APS. Livedo reticularis or racemosa is commonly seen in APS, but it is one of the least specific findings. Other diseases are less commonly seen, in either their idiopathic or APS-associated form, but are more suggestive of APS. APS should be considered in patients who may appear to have idiopathic livedo reticularis with cerebrovascular accidents (Sneddons syndrome), atrophie blanche, livedoid vasculitis, malignant atrophic papulosis, or anetoderma. Finally, retiform (branching, stellate) purpura or necrosis is perhaps the most characteristic cutaneous lesion of many different cutaneous microvascular occlusion syndromes, including APS.

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.

Human parvovirus B19-induced vesiculopustular skin eruption

Erythema infectiosum, fifth disease, is a usually benign macular or maculopapular exanthem of childhood caused by the human parvovirus B19. A 27-year-old woman with a serologically documented human parvovirus infection who presented with a hemorrhagic exanthem and enanthem with areas of pustules and pseudo-pustules is described. The histologic findings were unusual because they combined the histologic features of morbilliform and vesiculopustular viral lesions. This case serves to underscore the occurrence of human parvovirus infection in adults. Further, it demonstrates the need to include parvovirus infection in the differential diagnosis of virally induced vesiculopustular skin eruptions.

Myeloma, paraproteinemias, and the skin

This review focuses on those systemic diseases or syndromes associated with monoclonal plasma cell disorders that may present with important cutaneous manifestations. Amyloidosis, POEMS syndrome, cutaneous plasmacytoma, xanthomas, benign hypergammaglobulinemic purpura of Waldenström, and scleromyxedema are emphasized.

Cutaneous angiomyolipoma : a light-microscopic, immunohistochemical, and electron-microscopic study

We report a case of cutaneous angiomyolipoma found on the helix of a 67-year-old man. The lesion was studied by routine light microscopy, special stains, immunohistochemical methods, and electron microscopy. Histologic examination showed a well-circumscribed nodule in the dermis composed of an intimate mixture of blood vessels, smooth muscle, and mature fat. These components were confirmed by special stains, immunohistochemistry, and electron microscopy. We concluded that the unique features of this lesion distinguish it from other lesions such as angiomyoma, angiolipoma, and other mixed mesenchymal tumors. This report demonstrates that the features considered diagnostic of angiomyolipoma can occur in extrarenal sites and, therefore, this diagnosis cannot be excluded on the basis of site alone.

Successful treatment of hypertrophic lupus erythematosus with isotretinoin

A patient with systemic lupus erythematosus had the additional finding of hypertrophic lupus erythematosus. The lesions cleared with an 11-week course of isotretinoin alone. She has remained without recurrence for 9 months. This is the first reported case of total resolution of hypertrophic lupus erythematosus with a short course of isotretinoin.

Hematologic Safety of Dapsone Gel, 5%, for Topical Treatment of Acne Vulgaris

OBJECTIVE To evaluate the risk of hemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency who were treated for acne vulgaris with either dapsone gel, 5% (dapsone gel), or vehicle gel. DESIGN Double-blind, randomized, vehicle-controlled, crossover study. SETTING Referral centers and private practice. PARTICIPANTS Sixty-four subjects 12 years or older with G6PD deficiency and acne vulgaris. Intervention Subjects were equally randomized to 1 of 2 sequences of 12-week treatment periods (vehicle followed by dapsone gel or dapsone gel followed by vehicle). The washout period was 2 weeks. Treatments were applied twice daily to the face and to other acne-affected areas of the neck, upper chest, upper back, and shoulders as required. MAIN OUTCOME MEASURES Results of clinical chemical analysis and hematology values; plasma dapsone and N-acetyl dapsone concentrations; spontaneous reports of adverse events. RESULTS A 0.32-g/dL decrease in hemoglobin concentration occurred from baseline to 2 weeks during dapsone gel treatment. This was not accompanied by changes in other laboratory parameters, including reticulocytes, haptoglobin, bilirubin, and lactate dehydrogenase levels, and was not apparent at 12 weeks as treatment continued. The number of subjects with a 1-g/dL drop in hemoglobin concentration was similar between treatment groups at both week 2 and week 12. The largest drops in hemoglobin concentration were 1.7 g/dL in the vehicle gel treatment group and 1.5 g/dL in the dapsone gel treatment group. No clinical signs or symptoms of hemolytic anemia were noted. CONCLUSIONS After treatment with dapsone gel, 5%, no clinical or laboratory evidence of drug-induced hemolytic anemia was noted in G6PD-deficient subjects with acne vulgaris. Trial Registration clinicaltrials.gov Identifier: NCT00243542.

Granulomatous mycosis fungoides. Clinicopathologic study of two cases.

Granulomatous mycosis fungoides is a rare form of mycosis fungoides with controversial histogenesis. Early reports seemed to indicate a favorable prognosis for these patients. We report two cases of granulomatous mycosis fungoides, both of which had other unusual clinical features. The cases were studied with routine light microscopy, immunohistochemistry, electron microscopy, and gene probe studies. Despite some clinical and histopathologic similarities, the results of the immunohistochemical and molecular biologic studies were diverse. These results suggest that granulomatous mycosis fungoides does not define a single subset of cases, immunophenotypically or biologically.

Xanthoma disseminatum and Waldenstrom's macroglobulinemia

A 71-year-old woman had a 7-month history of multiple asymptomatic papules on the upper part of the body. The clinical picture and histopathologic findings confirmed the diagnosis of xanthoma disseminatum. Further studies revealed Waldenströms macroglobulinemia. Treatment with chlorambucil and prednisone led to a dramatic reduction in her paraprotein level. In addition, cutaneous lesions improved and new lesions stopped appearing. Treatment of selected papules by cryotherapy or intralesional corticosteroid injection provided further improvement. This case is notable because (1) it is the first report of xanthoma disseminatum in a patient with Waldenströms macroglobulinemia and (2) there was an unusually good response to therapy.