Background
Erythema induratum, also known as nodular vasculitis or Bazin disease, is categorized as a tuberculid skin eruption, which is a group of skin conditions associated with an underlying or silent focus of tuberculosis (TB). They are sequelae of immunologic reactions to hematogenously dispersed antigenic components of Mycobacterium tuberculosis. [1] Other members of the tuberculid group include papulonecrotic tuberculid, lichen scrofulosorum, and vascular reactions caused by tuberculosis, namely, nodular tuberculid and nodular granulomatous phlebitis, all of which are distinct from erythema induratum. [2]
In 1861, Ernest Bazin gave the name erythema induratum to a nodular eruption that occurred on the lower legs of young women with tuberculosis. Although nodular vasculitis and erythema induratum (Bazin disease) have historically been considered synonymous, the terms erythema induratum and Bazin disease are currently only used for cases of nodular vasculitis that are associated with M tuberculosis infection. [3] The term nodular vasculitis was coined in 1945 to describe chronic inflammatory nodules of the legs that showed histopathologic changes similar to those of erythema induratum; that is, nodular vasculitis is a form of lobular panniculitis associated with subcutaneous blood vessel vasculitis that leads to ischemic changes. [3]
Although erythema induratum and nodular vasculitis were once considered to be the same disease, nodular vasculitis is now considered a multifactorial syndrome of lobular panniculitis in which tuberculosis may or may not be one of a multitude of etiologic components. Currently, erythema induratum/nodular vasculitis complex is classified into three variants: tuberculosis-associated erythema induratum (Bazin disease), erythema induratum associated with other diseases and drugs, and idiopathic erythema induratum. [4]
Related Medscape Drugs & Diseases articles include Tuberculosis and Pediatric Tuberculosis.
Pathophysiology
The pathogenesis of erythema induratum is not completely understood. The morphologic, molecular, and clinical data suggest that erythema induratum and nodular vasculitis represent a common inflammatory pathway: an immune-mediated hypersensitivity reaction to endogenous or exogenous antigens, one such antigen being M tuberculosis. Histologically, erythema induratum lesions demonstrate a mixed granulomatous inflammatory process triggered by M tuberculosis or other antigens. Because erythema induratum involves vasculitis, it is likely that endothelial antigens are a target of cell-mediated cytotoxic processes occurring in erythema induratum. Patients with erythema induratum have a positive tuberculin skin test result and a marked increase in their peripheral T-lymphocyte response to the purified protein derivative (PPD) of tuberculin, which can cause a delayed-type hypersensitivity reaction. Results of the enzyme-linked immunosorbent assay–based interferon-gamma release assay blood test for tuberculosis are often positive in patients with erythema induratum, again suggesting that erythema induratum is a hypersensitivity reaction to a systemic infection, and that erythema induratum has features of both type III (immune-complex–mediated) and type IV (delayed-type) hypersensitivity reactions.
Etiology
The etiology of erythema induratum remains poorly understood, although there is consensus that the erythema induratum/nodular vasculitis complex is a multifactorial, immune-mediated hypersensitivity reaction. More specifically, erythema induratum is thought to result from an immune-complex–mediated (type III hypersensitivity) vascular injury due to bacterial antigens. [3] Immunoglobulins, complement, and bacterial antigens have all been identified by immunofluorescence, and in some cases mycobacterial DNA sequences have been found by polymerase chain reaction. [3] Infection with M tuberculosis is considered to be an etiologic factor for erythema induratum that is associated with tuberculosis (Bazin disease), and, based on published reports, latent or active TB infection is the most common reported identifiable cause of erythema induratum. In a retrospective study of 65 patients with histologically diagnosed erythema induratum in Spain between 1976 and 1994, 89% had a positive tuberculin skin test. [5] Disease associations besides TB are more rare but have been documented in case reports. Examples include the following:
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Superficial thrombophlebitis [6]
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Hematologic disorders such as chronic lymphocytic leukemia and antiphospholipid antibody syndrome [14]
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Bacterial infections, including Nocardia, Pseudomonas, Fusarium, and Chlamydia pneumoniae [17] infections
Erythema induratum has also been associated with certain drugs in case reports, such as etanercept and propylthiouracil. [21, 22] In a patient treated for rheumatoid arthritis with certolizumab pegol, erythema induratum occurred together with new-onset TB lymphadenitis. [23] Additionally, recurrence of erythema induratum has also been reported during chemotherapy for breast cancer. [24]
A minority of cases of erythema induratum have no identifiable cause and are classified as idiopathic erythema induratum.
Epidemiology
Frequency
Erythema induratum is an uncommon disease, and it has been reported in the United States, Europe, Asia, Africa, and Australia. [6, 25, 26, 27, 28]
United States
Isolated cases of erythema induratum have been reported in the United States.
International
While nodular vasculitis is quite common, particularly in Europe, erythema induratum is rare in Western countries. Erythema induratum is still prevalent in India, Hong Kong, and some areas of South Africa. [29]
Sex
Eighty percent of patient with erythema induratum are middle-aged women; however, both females and males can be affected. [2] All variants of erythema induratum (TB-associated and non–TB-associated) are vastly more common in females.
Age
Although the age range for individuals affected by erythema induratum is variable, a large series of 86 erythema induratum patients found that the median age was 56 years (range, 23-81 y); another series of TB-associated erythema induratum found the mean age at presentation to be 37 years (range, 13-66 y). [6] Additionally, case reports have described erythema induratum in young children. [30]
Prognosis
The prognosis is good if properly treated. To date, no fatal cases of erythema induratum have been reported. However, the chronic, recurrent, painful nodules and resultant scarring can be a source of significant morbidity.
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This patient exhibited tender, erythematous nodules confined to the lower third of the legs.
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Vasculitis and granulomatous inflammation in the dermis and subcutaneous fat tissues.
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Evidence of panniculitis exhibiting lobular, granulomatous, and lymphohistiocytic inflammation.
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A positive Mantoux test reaction in a patient with erythema induratum.
