Erythema nodosum

Erythema nodosum presents a typical clinical picture. There are multiple tender subcutaneous nodules of inflammatory nature mainly on the lower parts of the legs and occasionally in other sites such as the arms, the trunk, or the external ear. Fever, leukocytosis, and a rise in ESR accompany the acute skin lesions, which usually subside within 2-3 weeks, although they may recur and may become chronic. 

The histological picture is characterized by inflammation localized in the connective tissue of the subcutis. Initially there is infiltration by granulocytes together with fibrin deposition and erythrocyte diapedesis later there are granulomatous lesions (Miescher 1947). 

It is generally accepted that erythema nodosum is of allergic origin, but the immunological mechanism is not understood. Among the possibilites suggested are reactions of the Arthus type, the cellular type (type IV), or mixed forms of the two (Haustein and Klug 1977). 

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Blood dyscrasias are quite uncommon, but if they occur may be serious enough to cause discontinuance of the therapy. Both topical and systemic adrninistration of sulfas can cause hypersensitivity reactions, such as urticaria, exfoHative dermatitis, photosensiti2ation, erythema nodosum, and in its most severe form, erythema multiformexudativum. (Stevens-Johnson syndrome). In general, however, use of sulfonamide therapy is considered relatively safe. 

NSAIDs can induce a number of other adverse reactions, including bleeding disorders, anemia, thrombocytopenia, erythema nodosum, erythema multiforme, fixed drug eruptions, toxic epidermal necrolysis, Stevens-Johnson syndrome, leukocytocla-sitc vasculitis, recurrent fever with exanthema and, of course, the well-known gastric cytotoxicity. 

Patients may manifest extraintestinal symptoms of IBD, such as arthritis, primary sclerosing cholangitis, erythema nodosum, and pyoderma gangrenosum, among others. 

The most frequent adverse effects are local reactions at the injection site (pain, tenderness, erythema, swelling, and pruritus), fevers (greater than 37.5°C or 99.5°F), headaches, dizziness, and irritability. Anaphylaxis and hypersensitivity reactions have been reported rarely and occur within a few hours after vaccine administration. In rare instances, a serum sickness-like apparent hypersensitivity syndrome (arthralgia, urticaria, ecchymoses, erythema multiforme, and erythema nodosum) has been... 

Ocular complications (iritis, episcleritis, and conjunctivitis) occur in up to 10% of patients. Five percent to 10% of patients experience dermatologic or mucosal complications (erythema nodosum, pyoderma gangrenosum, aphthous stomatitis). 

Dermatologic findings with erythema nodosum, pyoderma gangrenosum, or aphthous ulceration Laboratory tests... 

The common systemic manifestations of IBD include arthritis, anemia, skin manifestations such as erythema nodosum and pyoderma gangrenosum, uveitis, and liver disease. 

Valley fever is a syndrome characterized by erythema nodosum and erythema multiforme of the upper trunk and extremities in association with diffuse joint aches or fever. Valley fever occurs in approximately 25% of infected persons, although, more commonly, a diffuse mild erythroderma or maculopapular rash is observed. 

Thalidomide (USA) a- (N-phthalimido) glutarimide TNF expression inhibitor Erythema nodosum leprosum, cGVHD... 

Dermafo/og/c. Alopecia, balanitis, erythema multiforme, erythema nodosum, fixed drug eruptions, hyperpigmentation of the nails, injection site erythema and injection site pain, maculopapular and erythematous rashes, photosensitivity, pruritus, skin and mucus membrane pigmentation, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis. 

Gastrointestinal disturbances are common. Its adverse reactions also include severe hemolytic anemia in people with G6PD deficiency. Skin reactions vary from erythema nodosum to toxic epidermal necrolysis. However its most serious adverse reaction is potentially fatal agranulocytosis. 

Clofazimine is a phenazine dye with some my-cobactericidal activity. It is only used in combination with dapsone to reduce the emerging resistance against dapsone. Its efficacy in the management of erythema nodosum leprosum is based on its antiinflammatory activity. 

In 1998, the FDA approved the use of thalidomide for the treatment of lesions associated with erythema nodosum leprosum. Because of thalidomide s potential for causing birth defects, the distribution of thalidomide was permitted only under tightly controlled conditions. Nevertheless, because of its use for patients with leprosy thalidomide has been identified again as a current teratogen, now in South America. 

Thalidomide is approved for use in the United States for the treatment of cutaneous manifestations of erythema nodosum leprosum, a potentially life-threatening systemic vasculitis that occurs in some patients with leprosy. Although not approved for other indications, thalidomide has also been shown to be very effective in the management of Behget s disease, HIV-related mucosal ulceration (aphthosis), and select cases of lupus erythematosus. 

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. 

Erythema nodosum PO 100-200 mg/day for up to 3 mo, then 100 mg/day. Contraindications None known Side Effects... 

Recently, thalidomide (50-100 mg capsule form, approved by FDA), an immunomodulatory agent is used in erythema nodosum leprosum (ENL) which is a complication of leprosy occurring in approximately one half of borderline lepromatous and lepromatous leprosy patients. 

In addition to the above effects, a number of other adverse reactions have been reported for which a causal relation has not been established. These include alopecia, erythema multiforme, erythema nodosum, and other skin disorders. 

Note Thalidomide is labeled for use only in erythema nodosum leprosum in the USA Trastuzumab (Herceptin)... 

Thalidomide Erythema nodosum leprosum See also Chapters 47 and 55. 

Three patients developed erythema nodosum during estrogen replacement therapy (60). 

There is a possible association of oral contraceptives with erythema nodosum, which has been linked to the use of either estrogens or progestogens or a combination of the two however, probably neither hormone directly causes the condition but merely creates a fertile background for its generation by other antigens. 

Erythema nodosum associated with lupus erythematosus cells has been described as an adverse effect of potassium perchlorate (SED-8, 897) (1). 

A 33-year-old woman developed acute pancreatitis together with mild cholestatic hepatitis and erythema nodosum 1 month after starting carbimazole for Graves disease rechallenge with a single dose of carbimazole (10 mg) 7 days after initial recovery led to a further episode of acute pancreatitis, from which she recovered (54). 

Marazuela M, Sanchez de Paco G, Jimenez I, Carraro R, Fernandez-Herrera J, Pajares JM, Gomez-Pan A. Acute pancreatitis, hepatic cholestasis, and erythema nodosum induced by carbimazole treatment for Graves disease. Endocr J 2002 49(3) 315-8. 

Allergic skin reactions have been described with all sulfonylureas. They include pruritic rashes, erythema nodosum, urticaria, blisters (100), erythema multiforme, exfoliative dermatitis, Quincke s edema, erythroderma, and itching, while lichenoid drug reactions with ulceration have occurred after chlorpropamide and tolazamide (124). More generalized hypersensitivity reactions may prove fatal, but rarely. 

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