BASICS
DESCRIPTION
- Erythema induratum of Bazin (EIB) is a chronic, nodular eruption that usually occurs on the lower legs of otherwise heavyset women.
- EIB is a cutaneous manifestation of tuberculin hypersensitivity in association with Mycobacterium tuberculosis (TB) infection (e.g., tuberculoid).
- Currently, the term "nodular vasculitis"Ł (NV) is often used as a synonym for EIB, although some authors make a distinction between the two conditions.
- EIB for lesions secondary to mycobacteria
- NV for noninfectious variant (e.g., Crohn disease)
- EIB most closely resembles erythema nodosum (EN) because there is overlap in clinical presentation and histologic features.
- After treatment of any identified potential etiologies, therapeutic options are similar for both EIB and EN, which are forms of panniculitis.
EPIDEMIOLOGY
Incidence
- Although NV is quite common, erythema induratum is rare other than in India, Hong Kong, and some areas of South Africa.
- Most common (86%) form of cutaneous TB (tuberculid) in Hong Kong found between 1993 and 2002.
- Predominant age: 13 to 66 years (mean 37 years)
- Predominant sex: female (80-90%) > male
ETIOLOGY AND PATHOPHYSIOLOGY
- The morphologic, molecular, and clinical data suggest that EIB and NV represent a common inflammatory pathway, that is, a hypersensitivity reaction (type III or IV) to endogenous or exogenous antigens, such as the tubercle bacillus.
- A causal relationship between EIB and TB is circumstantial and based on the following:
- High degree of hypersensitivity to purified protein derivative (PPD), often marked
- Frequent personal or family history of TB
- Presence of active TB foci
- Occasional coexistence with other tuberculids in the same patient
- Response to anti-TB treatment
- Results from the enzyme-linked immunosorbent assay-based (interferon-╬│ release assays or IGRA), such as QuantiFERON-TB Gold In-Tube and T-SPOT TB blood tests commonly are positive in patients with EIB.
- EIB has been associated with other atypical mycobacteria.
Genetics
No known genetic predisposition á
RISK FACTORS
- Prior or current infection with M. tuberculosis
- Age <40 years
- Female gender
- Obesity
- Bacille Calmette-Gu ęrin (BCG) vaccination
- Residence in Asia (e.g., especially India and Hong Kong) and South Africa
- HIV
- Hepatitis C
- Crohn disease
GENERAL PREVENTION
- BCG vaccination has reduced cases of M. tuberculosis infection worldwide. However, vaccine risks include complications, such as subcutaneous abscesses including EIB, localized or generalized cutaneous tuberculids, local inflammation, fever, and spread of TB to distant organs.
- Safe sex precautions, including condom use
- Counsel regarding not sharing needles in order to prevent HIV or hepatitis C transmission.
COMMONLY ASSOCIATED CONDITIONS
- A past or present history of TB at an extracutaneous site occurs in about 50% of patients.
- Pulmonary TB (PTB) is most common.
- TB cervical lymphadenitis is the next most common.
- Important to consider if HIV infection is present when TB and NV are present.
- Other tuberculoids (e.g., lupus vulgaris)
- Hepatitis C
DIAGNOSIS
HISTORY
- Patients report experiencing mildly tender recurrent nodules, typically on the legs.
- Patients may note a chronic or relapsing course with postinflammatory hyperpigmentation at former lesion sites.
- Cold weather is often cited as an inciting factor, but that may simply be due to its association with similar conditions such as cold panniculitis and EN.
- Although patients are otherwise healthy and there are no accompanying systemic symptoms (e.g., fever, night sweats, weight loss), it is important to obtain a complete history to review for infection with TB including the following:
- TB exposure contacts
- Recent travel to Asia or South Africa
- BCG vaccine status
- HIV status
- History of IV drug abuse and/or high-risk sexual behavior (e.g., HIV and hepatitis C)
- Gastrointestinal (GI) complaints (e.g., Crohn disease)
- Inquire about drug history, as glucocorticoids, chemotherapy, immunomodulating drugs for autoimmune diseases (e.g., psoriasis, organ transplantation), and radiation therapy can all predispose to TB infection.
PHYSICAL EXAM
- Pertinent findings include the following:
- Tender, erythematous, or violaceous nodules 1- to 2-cm in diameter are present on the calves, and less frequently the anterolateral areas of the legs including the ankles.
- Lesions are usually bilateral.
- Most frequently seen in patients with fatty legs, diffuse erythema, cutis marmorata, and follicular hyperkeratosis.
- Uncommonly, the trunk, buttocks, thighs, and arms can be involved. Disseminated erythema induratum has been reported.
- Lesions may ulcerate with bluish borders and display overlying crust with rolled erythematous blue-tinged border.
- Healed lesions leave postinflammatory hyperpigmentation and occasionally atrophic and depressed hyperpigmented scars.
- Leg edema may be present.
- Cervical lymph nodes, thyroid, lungs, heart, abdomen, and scrotum should also be examined to rule out active infection. Cardiac echo can be employed to rule-out TB pericarditis in endemic areas.
DIFFERENTIAL DIAGNOSIS
- NV
- EN
- Other tuberculoids (e.g., scrofuloderma, lichen scrofulosorum and papulonecrotic tuberculid, leprosy)
- Cutaneous polyarteritis nodosa
- Cold panniculitis
- Pancreatic panniculitis
- Lupus profundus
- Subcutaneous sarcoid
- Cutaneous T-cell lymphoma
- Ecthyma gangrenosum (e.g., associated with a Pseudomonas aeruginosa bacteremia in immunocompromised patients)
- Superficial thrombophlebitis of the lower legs
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Complete blood count (CBC) with differential
- Erythrocyte sedimentation rate (ESR) (elevated)
- Tuberculin PPD skin test
- IGRA (QuantiFERON-TB Gold In-Tube and T-SPOT blood tests) are assays that assess for latent TB infection (1)[A].
- A chest radiograph or computed tomography (CT) to search for active or prior infection.
- Liver function tests and hepatitis C virus serology
Diagnostic Procedures/Other
- Mycobacterial culture, stained smears, and histopathology often fail to detect the presence of M. tuberculosis due to the relatively low numbers of organisms in lesional tissue (2)[B].
- An excisional biopsy containing adequate subcutaneous fat is recommended for histologic analysis.
- Polymerase chain reaction (PCR) may identify mycobacterial DNA in lesional tissue from formalin-fixed, paraffin-embedded specimens (77% of cases) (3)[B].
- PCR can be applied to differentiating NV from EIB because the demonstration of mycobacteria emerges as the only reliable criterion in EIB.
- Results are inconsistent (4)[C]. A negative PCR finding does not exclude a diagnosis of EIB as factors, such as patient history, constitutional symptoms, PPD, QuantiFERON-TB, or radiographic evidence, and response to anti-TB therapy must also be considered as evidence of M. tuberculosis infection.
Test Interpretation
- Some patients are highly sensitive to tuberculin PPD with ulceration occurring at the test site.
- Histologic findings most commonly show diffuse septolobular panniculitis with primary neutrophilic vasculitis of nearby vessels, predominantly small venules of the fat lobule (5)[B].
- There are areas of fat necrosis with granulomatous inflammatory infiltrates showing epithelioid cells, foamy histiocytes, and Langerhans-type giant cells.
- There are varying degrees of acute and chronic inflammation, coagulative and caseation-like necrosis, and poorly developed granulomas.
- Presence of vasculitis is not a diagnostic requisite (e.g., present in only 91%); however, the simultaneous presence of both vasculitis and granulomas suggests a role for both type III and type IV hypersensitivities in the pathogenesis of EIB.
- Epidermis may be intact or ulcerated.
TREATMENT
GENERAL MEASURES
- Rest
- Compression stockings should be worn to prevent edema and increase healing of lesions.
- Ulcerative lesions should be kept clean by washing legs or affected areas with warm water and mild soap.
MEDICATION
- Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful drugs to enhance analgesia and resolution (5)[C].
- Steroids are generally not recommended.
- EIB is treated with multidrug antituberculous therapy (6)[C]. Refer to current Centers for Disease Control and Prevention (CDC) guidelines for dosing regimen and precautions relevant to antituberculous therapy.
- Some favor anti-TB treatment even if association to TB has not been proved. However, anti-TB therapy is not benign and serious side effects such as hepatotoxicity and severe persistent peripheral neuropathy unresponsive to vitamin B6 may warrant cessation of therapy in instances where TB has not been definitively diagnosed.
- Treatments used for EN and hypersensitivity reactions found in leprosy are often employed for EIB. These include the following:
- Potassium iodide (360 to 900 mg daily in 3 divided doses) is sometimes applied, with highest efficacy in those receiving it shortly after the initial onset of induratum (7)[C].
- Colchicine (0.5 to 1.0 mg/day) (8)[C]
- Dapsone, thalidomide, mycophenolate mofetil, and oral gold (5) have been may be helpful according to isolated case reports.
- Hepatitis C-associated erythema induratum has responded to interferon and ribavirin.
ISSUES FOR REFERRAL
Dermatologist and infectious disease consultation á
SURGERY/OTHER PROCEDURES
Surgery is generally not indicated for the treatment of erythema induratum. á
INPATIENT CONSIDERATIONS
- The workup and diagnosis of erythema induratum is outpatient.
- Initial anti-TB sometimes requires hospital admission in patients with active PTB.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Patients should be seen as needed for persistent or recurrent flares of erythema induratum and to address compliance and/or changes to drug therapy.
- Assess for signs of secondary infection in the presence of ulcerations.
DIET
No special diet is required in this patient population. á
PROGNOSIS
- Untreated, the disease runs a relapsing course chronic course with recurrent crops of new lesions arising every 3 to 4 months over the course of many years depending on host hypersensitivity to tuberculin antigens and immune status.
- Prognosis is good with compliance to antituberculous therapy, and some patients may even experience spontaneous resolution of lesions.
COMPLICATIONS
- Ulceration of nodules can result in secondary infection and cellulitis.
- Lesions heal with permanent, depressed, and hyperpigmented scars.
REFERENCES
11 Mazurek áGH, Jereb áJ, Lobue áP, et al. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm Rep. 2005;54(RR-15):49-55.22 Mascar │ áJMJr, Baselga áE. Erythema induratum of bazin. Dermatol Clin. 2008;26(4):439-445.33 Schneider áJW, Jordaan áHF, Geiger áDH, et al. Erythema induratum of Bazin. A clinicopathological study of 20 cases and detection of Mycobacterium tuberculosis DNA in skin lesions by polymerase chain reaction. Am J Dermatopathol. 1995;17(4):350-356.44 Tan áSH, Tan áHH, Sun áYJ, et al. Clinical utility of polyermerase chain reaction in the detection of Mycobacterium tuberculosis in different types of cutaneous tuberculosis and tuberculids. Ann Acad Med Singapore. 2001;30(1):3-10.55 Gilchrist áH, Patterson áJW. Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management. Dermatol Ther. 2010;23(4):320-327.66 Requena áL, Yus áES, Kutzner áH. Panniculitis. In: Wolff áK, Goldsmith áLA, Katz áSI, et al, eds. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, NY: McGraw Hill; 2008;1:569.77 Requena áL, Requena áC. Erythema nodosum. Dermatol Online J. 2002;8(1):4.88 Davatchi áF, Sadeghi Abdollahi áB, Tehrani Banihashemi áA, et al. Colchicine versus placebo in Beh žet's disease: randomized, double-blind, controlled crossover trial. Mod Rheumatol. 2009;19(5):542-549.
ADDITIONAL READING
- Diel áR, Loddenkemper áR, Nienhaus áA. Evidence-based comparison of commercial interferon-gamma release assays for detecting active TB: a metaanalysis. Chest. 2010;137(4):952-968.
- Fernandes áSS, Carvalho áJ, Leite áS, et al. Erythema induratum and chronic hepatitis C infection. J Clin Virol. 2009;44(4):333-336.
- Inoue áT, Fukumoto áT, Ansai áS, et al. Erythema induratum of Bazin in an infant after Bacille Calmette-Guerin vaccination. J Dermatol. 2006;33(4):268-272.
- Vera-Kellet áC, Peters áL, Elwood áK, et al. Usefulness of interferon-╬│ release assays in the diagnosis of erythema induratum. Arch Dermatol. 2011;147(8):949-952.
CODES
ICD10
A18.4 Tuberculosis of skin and subcutaneous tissue á
ICD9
017.10 Erythema nodosum with hypersensitivity reaction in tuberculosis, unspecified á
SNOMED
- Erythema induratum
- Nodular vasculitis (disorder)
CLINICAL PEARLS
- Erythema induratum is a chronic nodular eruption of the subcutaneous tissue found in lower legs of otherwise heavyset women.
- Seen predominantly in patients living in or from India, Hong Kong, and some areas of South Africa
- M. tuberculosis is the most common etiology.
- Treatment regimen usually involves multidrug anti-TB drugs to decrease recurrence rates.
- Diagnosis often made retrospectively, depending on the response to anti-TB treatment.
- Lesions heal with atrophic, depressed, hyperpigmented scars.
- Adjunctive therapeutic options are similar for both erythema induratum and EN.