Leukocytoclastic vasculitis

Vasculitis ischemic ulcers, skin lesions, leukocytoclastic vasculitis... 

Dapsone is approved for the treatment of an autoimmune blistering skin disease, dermatitis herpetiformis. This intensely pruritic eruption is characterized histologically by a dense dermal infiltration of neutrophils and subepidermal blisters. Other skin diseases in which dapsone is helpful are linear immunoglobulin A (IgA) dermatosis, subcorneal pustular dermatosis, leukocytoclastic vasculitis, and a variety of rarer eruptions in which neutrophils predominate, including some forms of cutaneous lupus erythematosus. 

The incidence of upper gastrointestinal bleeding in over-the-counter use is low but still double that of over-the-counter ibuprofen (perhaps due to a dose effect). Rare cases of allergic pneumonitis, leukocytoclastic vasculitis, and pseudoporphyria as well as the common NSAID-associated adverse effects have been noted. 

An 84-year-old woman with polymyalgia rheumatica and a 79-year-old woman with undifferentiated connective tissue disease and leukocytoclastic vasculitis were given prednisolone 20 mg/day with subsequent dosage reductions. The first patient developed a raised purpuric rash and lymphedema of the left leg within 5 months and the second developed large purple nodules on the soles of her feet and the backs of her hands accompanied by periorbital and peripheral edema. Skin biopsies showed Kaposi s sarcoma, and both patients had raised IgG antibody titers to human herpesvirus-8. 

A 67-year-old woman developed Henoch-Schonlein purpura, with a leukocytoclastic vasculitis and joint pains, after taking anastrozole for 10 months the symptoms resolved within 2 weeks of withdrawal (34). 

ANCA-positive microscopic polyangiitis has been associated with propylthiouracil, with a fatal outcome despite treatment with glucocorticoids and cyclophosphamide (87). Another patient presented atypically with acute pericarditis 10 months after starting to take propylthiouracil 100 mg tds (88). Another patient developed ANCA-negative leukocytoclastic vasculitis of the skin (89). 

Leukocytoclastic vasculitis and pneumonitis have been attributed to metformin (110,111). 

Leukocytoclastic vasculitis has been attributed to human insulin. 

Mandrup-Poulsen T, Molvig J, Pildal J, Rasmussen AK, Andersen L, Skov BG, Petersen J. Leukocytoclastic vasculitis induced by subcutaneous injection of human insulin in a patient with type 1 diabetes and essential thrombocyte-mia. Diabetes Care 2002 25(l) 242-3. 

A 62-year-old woman with type 2 diabetes, hypertension, and chronic hepatitis C virus infection developed palpable purpura over her legs and buttocks 3 weeks after starting to take repaglinide 500 mg qds (52). The purpura ulcerated and became infected. Repaglinide was withdrawn and the purpura resolved. A biopsy showed leukocytoclastic vasculitis. 

Repaglinide, which is metabolized in the liver, is cleared more slowly in people with liver disease, and hepatitis C may have played a part in this case. Although hepatitis C can cause a leukocytoclastic vasculitis, the clinical correlation and the rapid disappearance of the purpura after the withdrawal of repaglinide makes it likely that this was an adverse effect of the drug. Caution with repaglinide in liver disease is important. 

Common adverse events include joint pain, joint swelling, and hypotension. Central intravenous line usage may be associated with pulmonary emboli and sepsis. Other events, such as nausea, rash, pruritus, flushing, and fever occurred in 1-6% of treatments in both sham and treatment groups in the double-blind trial. Rare leukocytoclastic vasculitis has been documented. 

Lithium is not an allergen. Allergic reactions that have been reported in patients taking lithium have been attributed to excipients in the formulation (432), as in a case of leukocytoclastic vasculitis (433). 

Lowry MD, Hudson CF, Callen JP. Leukocytoclastic vasculitis caused by drug additives. J Am Acad Dermatol 1994 30(5 Part 2) 854-5. 

A 30-year-old man developed destructive rhinitis due to cocaine abuse after initially presenting with Henoch-Schonlein purpura (121). Cocaine use can mimic vasculitis and is often accompanied by positive ANCAs. Cocaine-induced midline destructive lesions are characterized by mucosal damage and ischemic necrosis of the nasal septum. Histopathological similarity to leukocytoclastic vasculitis and the presence of PR3-ANCA can lead to confusion between Wegener s granulomatosis and cocaine-induced midline destructive lesions. 

Leukocytoclastic vasculitis has been reported with sotalol (286). 

A progressive cutaneous vasculitis occurred in a 66-year-old man taking sotalol for prevention of a symptomatic atrial fibrillation. After 7 days he noted a petechial eruption on his wrists and ankles. This progressed during the next days to palpable purpura on the hands, wrists, ankles, and feet. A biopsy specimen showed changes consistent with leukocytoclastic vasculitis. After withdrawal of sotalol the skin rash cleared completely without any other intervention. 

Other beta-blockers associated with leukocytoclastic vasculitis include acebutolol, alprenolol, practolol, and propranolol. 

Rustmann WC, Carpenter MT, Harmon C, Botti CF. Leukocytoclastic vasculitis associated with sotalol therapy. J Am Acad Dermatol 1998 38(1) 111-12. 

Generalized pustular eruptions, histologically presenting as leukocytoclastic vasculitis with neutrophils forming subcorneal pustules, have been reported with different cephalosporins, such as cefaclor (130), cefazolin (131,132), cefalexin (133), and cefradine (134). 

A 44-year-old man, having taken various antiretroviral drugs, started to take efavirenz 5 days later he developed palpable purpura on both legs, with pruritus. His white cell count was 14.4 x 10 /1 and a skin biopsy showed a leukocytoclastic vasculitis. Efavirenz was withdrawn and he was given prednisolone for 3 days the lesions disappeared, leaving only minimal hyperpigmentation. 

Domingo P, Barcelo M. Efavirenz-induced leukocytoclastic vasculitis. Arch Intern Med 2002 162(3) 355-6. 

One patient who had separate episodes of vascular purpura during each of three sequences of treatment with etanercept, with leukocytoclastic vasculitis during the third episode, later developed similar cutaneous lesions after a third injection of infliximab (19). 

Leukocytoclastic vasculitis caused by flurbiprofen has been observed in a patient with rheumatoid arthritis (SEDA-15,101). 

Leukocytoclastic vasculitis is a well-described and confirmed adverse effect of G-CSF, as documented in several reports, with recurrence after renewed administration of G-CSF (SEDA-19,343). Most cases were confined to the skin, and renal insufficiency with hematuria and proteinuria was noted in only very few patients. Based on 18 cases reported in the hterature or to the manufacturers, vasculitis was thought to have occurred in 6% of patients with chronic benign neutropenia, but in only six of about 200 000 patients with mahgnant disease (68). Vasculitis usually developed when the neutrophil count rose above 800 X 10 /1, suggesting that an increase in neutrophil count may play a role in necrotic vasculitis. Against this background, the occurrence of vascuhtis is not considered as treatment-hmiting and does not preclude further G-CSF administration if the absolute neutrophil count is lower than 1000 x 10 /1. 

A 20-year-old woman developed chronic rhinitis 1 month after the last dose of hepatitis B, followed about 1 year later by severe asthma, nasal polyposis, and petechial purpura in her fingernail beds and on her feet. A skin biopsy from the left leg showed infiltrates consistent with leukocytoclastic vasculitis. 

The administration of equine or other immunoglobulins is associated with a considerable risk of adverse effects and can produce virtually any type of early or late hypersensitivity reaction, ranging from asthma and urticaria to serum sickness and fatal anaphylaxis (103-106). Encephalitis (107), myocarditis (108), nephritis (109), and uveitis (110) can all be manifestations of such reactions. In one case, leukocytoclastic vasculitis was attributed to human immunoglobulin (96). 

Leukocytoclastic vasculitis has been attributed to levamisole in a 7-year-old boy with glucocorticoid-dependent nephrotic syndrome (44). 

Henoch-Schdnlein purpura developed in an 84-year-old Indian woman 10 days after she started to take clarithromycin (250 mg bd) for pneumonia (52). She was otherwise healthy and taking no regular medications. Histology confirmed a leukocytoclastic vasculitis of superficial vessels, with extravasation of erythrocytes, and direct immunofluorescence showed immunoglobulin A in superficial dermal vessels. Treatment with prednisone (1 mg/kg/day) was required. Most of the symptoms and signs resolved within a few days, but renal function remained impaired. 

The authors identified two previous case reports of clarithromycin-induced leukocytoclastic vasculitis. 

Isolated cutaneous leukocytoclastic vasculitis occurs infrequently in patients taking methotrexate, and an immediate-type hypersensitivity reaction has been thought to be involved, in view of prompt recurrence after drug readministration or a positive mast cell degranulation test as recorded in several patients (SEDA-21, 388) (SEDA-22, 417) (72). 

Halevy S, Giryes H, Avinoach I, Livni E, Sukenik S. Leukocytoclastic vasculitis induced by low-dose methotrexate in vitro evidence for an immunologic mechanism. J Eur Acad Dermatol Venereol 1998 10(l) 81-5. 

A leukocytoclastic vasculitis occurred in a 62-year-old woman with skin, peripheral nerve, and renal involvement (27). Long-term corticosteroid treatment caused gradually resolution. 

Schapira D, Balbir-Gurman A, Nahir AM. Naproxen-induced leukocytoclastic vasculitis, din Rheumatol 2000 19(3) 242-4. 

Leukocytoclastic vasculitis has been ascribed to nicotine patches in two patients (35). Two other patients developed vasculitis in association with the use of nicotine patches (36). The authors concluded that it was likely that the reactions in the two patients were related to the nicotine therapy. However, the possibility of a reaction to the vehicle (coconut oil and polymers) could not be excluded. 

Cutaneous leukocytoclastic vasculitis has been reported in a 71-year-old woman with epigastric pain who had taken omeprazole 20 mg/day for 4 weeks (26). She made a full recovery after omeprazole was withdrawn. 

Witzeus M, Moehler T, Nebeu K, Fruehauf S, Hartschuh W, Ho AD, Goldschmidt H. Developmeut of leukocytoclastic vasculitis iu a patieut with multiple myeloma duriug treatmeut with thahdomide. Auu Hematol 2004 83(7) 467-70. 

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