Erythema induratum: causes, symptoms, diagnosis, and treatment

Erythema induratum is characterized by bilateral, asymmetric, bright red, dark red, or purplish red, nodular lesions in the calves, thighs, and even upper limbs, with obvious tenderness, generally without pruritus, mainly in young females, and can be divided into erythema induratum of Bazin that is associated with tuberculosis and erythema induratum of Whitfield that is not associated with tuberculosis.


Causes

Patients are often accompanied by pulmonary tuberculosis, lymphatic tuberculosis, or other organ tuberculosis. Erythema induratum presents with tuberculoid infiltration, and caseous necrosis is often present, so that it has been considered cutaneous tuberculosis, but mycobacterium tuberculosis cannot be found. It is believed that erythema induratum is a subcutaneous arteriovenous vasculitis that causes adiponecrosis. However, it is also believed that erythema induratum results from a local allergic reaction initially, followed by a delayed hypersensitivity reaction, caused by release of mycobacterium tuberculosis from the blood vessels. Therefore, the disease may be a skin immune response due to various factors stimulating the immune system, more common in standing workers.


Signs and Symptoms

Several to several dozen, pea sized to finger sized indurations occur initially in the deep skin of the calf. Because the lesions are in the subcutis, the surface of the skin may be unchanged, but the indurations can be palpable. After few weeks, the nodules enlarge and adhere to the skin, inflammation spreads to the skin, and the affected skin turns into slightly elevated, sharply demarcated, fixed, solid, dark red to purplish blue plaques. Systemic symptoms are generally absent, subjective local varying degrees of tenderness, distending pain, and burning sensation are present, and patients have obvious swelling in lower legs especially when walking. The nodules can spontaneously regress, leaving reddish brown pigmentation. Sometimes the nodules fuse with each other, forming larger plaques. Some nodules can soften and rupture, forming deep ulcers with cliffy or undermined soft edges, surrounded by inflammatory infiltration, with base composed of soft dark red granulation tissue. Thin pus is discharged and the ulcers are refractory, leaving atrophic scars after healing.

The disease develops slowly. When the initial lesions subside or heal, new lesions occur, and indurations, ulcers, and scars are often simultaneous. Recurrence is often present, especially under cold conditions. The predilection site is mainly the flexion surfaces of calves, and the anterior calves, foot, and ankle joint can be invaded, causing the swollen ankle joint. Occasionally the upper limbs or other areas can be involved.


Histopathology

Epidermal atrophy, obvious vasculitis changes in the deep dermis and subcutaneous tissue, vascular endothelial swelling, degeneration, or hyperplasia, thrombosis, and luminal occlusion are present. Initial lymphocytes infiltration around the blood vessels and obvious caseous necrosis in the infiltrating focus are visible. Fat cells degeneration and necrosis, surrounded by proliferating macrophages, fibroblasts, and foreign body giant cells can be seen. The lesions are finally replaced by fibrous tissue, forming scars.


Diagnosis

On the basis of inflammatory nodules in the flexion surfaces of the calves in young females, symmetrical distribution, tenderness, ulcers after rupture of the nodules, and the results in pathological changes, diagnosis is not difficult.

Differential diagnosis

Erythema nodosum is manifested by red solid nodules in the extensor surfaces of the lower leg, obvious local pain and tenderness, without ulceration, with systemic symptoms such as joint pain, and short duration. The pathology is small focal infiltration. Caseous necrosis is absent, and tuberculous infiltration is less common.

Erythrocyanosis is manifested by symmetrical and diffuse cyanosis in the lower calves and skin temperature lower than normal, without nodules and ulcers. The disease is considered to be manifestations of endocrine disorders, and can be induced by cold.

Scrofuloderma is characterized by ulcers and sinus tracts resulting from cutaneous perforation caused by lymphatic tuberculosis or bone and joint tuberculosis, mostly in the neck and upper chest, often unilateral and asymmetric, rarely in the flexion surfaces of calves.

Syphilitic gumma often presents with asymmetrical, rapidly progressive, hard nodules, with sharp edges, with base composed of necrotic tissue and gummatous secretions, with history of sexual contacts, with positive results in serological test of syphilis.


Treatment

Topical 10% - 20% ichthammol ointment can be used for initial skin lesions, and gentamicin or other antibiotic ointment can be applied after rupture.

Intralesional injection of fluorinated steroids, such as triamcinolone acetonide suspension twice a week for 1 – 2 weeks, can be administered.

In erythema induratum of Bazin, systemic anti-tuberculosis treatment should be performed.

First-line anti-tuberculosis drugs include isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB). These drugs should be treated in combination.

Second-line anti-tuberculosis drugs are often used in drug-resistant tuberculosis patients or patients unable to tolerate first-line drugs, mainly including aminoglycosides and fluoroquinolones, such as streptomycin, kanamycin, amikacin, capreomycin, levofloxacin, and moxifloxacin. Aminoglycosides are only for parenteral use.

Other second-line drugs include ethionamide, cycloserine, and para-aminosalicylic acid, with anti-tuberculosis effect weaker than first-line drugs, with strong toxicity, but effective against drug-resistant tuberculosis.

Bedaquiline, delamanid, and sutezolid are new anti-tuberculosis drugs and are usually reserved for extensively drug-resistant tuberculosis, or patients unable to tolerate other second-line drugs.