Samuel L. Moschella

Clofazimine : a review of its medical uses and mechanisms of action

Clofazimine has been in clinical use for almost 40 years, but little is known of its mechanism of action. The primary indication for clofazimine is multibacillary leprosy, but it is useful in several infectious and noninfectious diseases, such as typical myocobacterial infections, rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe acne, pustular psoriasis, and discoid lupus erythematosus. Postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2. Clinical experience, possible mechanisms of action, and side effects of clofazimine are summarized.

Sarcoidosis: An updated review

Sarcoidosis, a multisystem disease of unknown cause characterized by the formation of noncaseating granulomas, may involve any organ of the body, but the commonest sites of predilection are the lungs, lymph nodes, skin, and eyes. Sarcoidosis can be associated with polyclonal hyperglobulinemia, hypercalcemia, hypercalciuria, circulating immune complexes, cutaneous anergy, and in vitro depressed cell-mediated immunity. Recent studies of the cellular composition and cellular interactions of sarcoid-involved tissue have resulted in some insight into the pathophysiology of the disease. In early stages the predominance of activated T-helper cells in affected sites may account for many of the immunologic aberrations. The production of macrophage chemotactic substances by these cells may be the initial stimulus for the formation of the granuloma. The natural history of the disease is highly variable; the acute forms tend to resolve spontaneously, whereas the chronic forms rarely involute. Although multiple therapeutic modalities have been used and some have reportedly been effective, systemic corticosteroids remain the most effective available therapeutic agents.

Neutrophilic eccrine hidradenitis: A distinctive rash associated with cytarabine therapy and acute leukemia

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.

Is there a role for infliximab in the current therapy of hidradenitis suppurativa? A report of three treated cases

Background  Hidradenitis suppurativa is one of the follicular occlusion diseases favoring the flexural areas of the body. Because of the past failure of medical therapy, surgery is today the definitive therapeutic approach. There is a need for effective medical anti‐inflammatory therapy to control the disease and minimize the pathologic and socioeconomic consequences of the disease process. Generally the patients fail to respond to topical or systemic antibiotics and retinoids. Temporary responses are achieved with intralesional steroids and cyclosporin.

Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-2004. A 68-year-old man with end-stage renal disease and thickening of the skin.

From the Department of Dermatology, Lahey Clinic, Burlington, Mass. (S.L.M.); the Division of Rheumatology, Department of Medicine (J.K.), the Department of Dermatology (B.T.M.), and the Division of Dermatopathology, Department of Pathology (V.L.), Massachusetts General Hospital; and the Departments of Dermatology (S.L.M., B.T.M.), Medicine (J.K.), and Pathology (V.L.), Harvard Medical School.

Collagenous vasculopathy: a report of three cases.

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy involving the superficial blood vessels that was initially reported in a 54‐year‐old male. We recently have identified this rarely reported entity in three Caucasian males. The first patient was a 59‐year‐old male with diabetes, hypertension and hypercholesterolemia who presented with multiple, red, blanchable, asymptomatic telangiectasias covering the extensor surface of the forearms, the lower abdomen and parts of the chest. The second patient was a 62‐year‐old male with psoriasis and extensive arthritis who presented with prominent telangiectasias on the left lateral distal thigh with mild overlying epidermal atrophy. The third patient was an 80‐year‐old male with atrial fibrillation who presented with blanching, telangiectatic areas on the abdomen, thighs and back. Histologically, the skin lesions showed ectatic superficial small blood vessels with laminated, hyalinized concretions around vessels that were highlighted with periodic acid‐Schiff staining following diastase digestion and reactive by immunohistochemical staining with an antibody to collagen type IV. CCV is a rare and poorly understood entity with distinct histopathological features that may clinically resemble generalized essential telangiectasia (GET), yet which may affect a different demographic population than GET. Awareness of this uncommon entity may further help to elucidate its etiology.

Case 35-2004: A 68-Year-Old Man with End-Stage Renal Disease and Thickening of the Skin

From the Department of Dermatology, Lahey Clinic, Burlington, Mass. (S.L.M.); the Division of Rheumatology, Department of Medicine (J.K.), the Department of Dermatology (B.T.M.), and the Division of Dermatopathology, Department of Pathology (V.L.), Massachusetts General Hospital; and the Departments of Dermatology (S.L.M., B.T.M.), Medicine (J.K.), and Pathology (V.L.), Harvard Medical School.

Double‐blind controlled crossover high‐dose study of Azaribine in psoriasis*

Azaribine used in high doses of 200 mg/kg a day is an effective agent in inducing temporary remissions in patients with severe psoriasis but potentially serious neurotoxicity may occur. Therapy should be initiated at lower doses of 125 mg/kg a day and advanced carefully only if clinical response does not ensue at the lower level.

Global dermatopathology: Hansen's disease – current concepts and challenges

Dr Martin Mihm is an internist, a dermatologist, a pathologist and a humanist. It is natural then that the complexity of Hansen’s disease would interest him not only as a medical subject but also as a deeply overwhelming human condition of global impact. His contributions to the field of Hansen’s disease are therefore not limited to academic ones such as a seminal paper describing in detail the light microscopy of erythema nodosum leprosum (ENL) that he coauthored with Dr George Murphy and others.1 Rather, and perhaps more importantly, he chose to experience the disease in the most direct way possible by traveling to Titigar, nearby Kolkata in India. There he volunteered with the ‘Missionaries of Charity Brothers’, a branch of Mother Teresa’s congregation. He worked for several weeks in the leprosarium cared by the brothers, where besides providing basic medical attention to those afflicted by Hansen’s disease, he trained the brothers how to use the extensive medical and surgical armamentarium donated to the mission. He catalogued the drugs and wrote detailed directions of how to diagnose and treat Hansen’s disease, lepra reactions, short and long-term complications, as well as other basic medical conditions afflicting these patients. He also went so far as to offer himself as a patient when he taught minor surgical procedures, allowing the brothers to remove some of his many moles. His time in India, he recounts, was one of the most significant medical experiences of his life. He often narrates this experience when emphasizing the magnitude of the effects of Hansen’s disease. It is noteworthy that in the year that we are celebrating Dr Mihm’s 75th birthday, with the plan to write this article already under way, he approached one of the authors (A. Piris) with his usual enthusiasm relating the recent finding of the oldest human skeleton with signs of Hansen’s disease, as well as the discovery of a new etiologic agent for Lepromatous Hansen’s disease. This anecdote highlights his ability to keep tabs on discoveries from disparate specialties, as he mainly focuses on pathology and dermatology at this time. With this brief introduction we would like to offer the reader a succinct account of the basic aspects of Hansen’s disease, with emphasis on the current status of the disease throughout the world and in the United States.

Case Report: Leishmanial Infections: A Consideration in Travellers Returning from Abroad

Seven cases of leishmaniasis, including a fatal case of visceral leishmaniasis and 6 cases of dermal leishmaniasis, were seen in Boston over a four-year period. Diagnosis was made by isolation of organisms in culture or by identification of organisms in stained preparations of tissue. Proper management of patients with leishmanial infections requires an appreciation of the geographical strain differences of each species.