Case Reports

Erythema Induratum of Bazin Presenting as Peripheral Neuropathy

Cutis. 2015 September;96(3):E1-E4

References

1. Segura S, Pujol RM, Trindade F, et al. Vasculitis in erythema induratum of Bazin: a histopathologic study of  101 biopsy specimens from 86 patients. J Am Acad  Dermatol. 2008;59:839-851.

2. Requena L, Sánchez Yus E. Panniculitis. part II. mostly lobular panniculitis. J Am Acad Dermatol. 2001;45:325-361.

3. Montgomery H, O’Leary PA, Barker NW. Nodular vascular disease of the legs: erythema induratum and allied conditions. JAMA. 1945;128:335-342.

4. Fernandes SS, Carvalho J, Leite S, et al. Erythema induratum and chronic hepatitis C infection [published online ahead of print February 23, 2009]. J Clin Virol. 2009;44:333-336.

5. Gilchrist H, Patterson JW. Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management. Dermatol Ther. 2010;23:320-327.

6. Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a practical case report and review for the dermatologist.  J Clin Aesthet Dermatol. 2009;2:19-27.

7. Schneider JW, Jordaan HF, Geiger DH, 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;17:350-356.

8. Lighter J, Tse DB, Li Y, et al. Erythema induratum of Bazin in a child: evidence for a cell-mediated  hyper-response to Mycobacterium tuberculosis. Pediatr Infect Dis J. 2009;28:326-328.

9. Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin  Dermatol. 2007;25:173-180.

10. Rademaker M, Lowe DG, Munro DD. Erythema induratum (Bazin’s disease). J Am Acad Dermatol. 1989;21  (4, pt 1):740-745.

11. Sharon V, Goodarzi H, Chambers CJ, et al. Erythema induratum of Bazin. Dermatol Online J. 2010;16:1.

12. Feiwel M, Munro DD. Diagnosis and treatment of erythema induratum (Bazin). Br Med J. 1965;1:1109-1111.

13. Lebel M, Lassonde M. Erythema induratum of Bazin. J Am Acad Dermatol. 1986;14(5, pt 1):738-742.

14. Silva MT, Antunes SL, Rolla VC, et al. Distal painful peripheral neuropathy associated with erythema induratum of Bazin. Eur J Neurol. 2006;13:e5-e6.

15. Jacinto SS, Nograles KB. Erythema induratum of bazin: role of polymerase chain reaction in diagnosis. Int J  Dermatol. 2003;42:380-381.

16. Ollert MW, Thomas P, Korting HC, et al. Erythema induratum of Bazin. evidence of T-lymphocyte hyperresponsiveness to purified protein derivative of tuberculin: report of two cases and treatment. Arch Dermatol. 1993;129:469-473.

17. Angus J, Roberts C, Kulkarni K, et al. Usefulness of the QuantiFERON test in the confirmation of latent tuberculosis in association with erythema induratum [published online ahead of print October 10, 2007]. Br J Dermatol. 2007;157:1293-1294.

18. Seckin D, Hízel N, Demirhan B, et al. The diagnostic value of polymerase chain reaction in erythema induratum of Bazin. Br J Dermatol. 1997;137:1011-1012.

19. Cannas A, Goletti D, Girardi E, et al. Mycobacterium tuberculosis DNA detection in soluble fraction of urine from pulmonary tuberculosis patients. Int J Tuberc Lung Dis. 2008;12:146-151.

20. Tan SH, Tan BH, Goh CL, et al. Detection of  Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids.  Int J Dermatol. 1999;38:122-127.

21. Baselga E, Margall N, Barnadas MA, et al.  Detection of Mycobacterium tuberculosis DNA in  lobular granulomatous panniculitis (erythema  induratum-nodular vasculitis). Arch Dermatol. 1997;133:457-462.

22. Cho KH, Lee DY, Kim CW. Erythema induratum of Bazin. Int J Dermatol. 1996;35:802-808.

23. Schulz EJ, Whiting DA. Treatment of erythema nodosum and nodular vasculitis with potassium iodide. Br J  Dermatol. 1976;94:75-78.

24. Horio T, Imamura S, Danno K, et al. Potassium iodide in the treatment of erythema nodosum and nodular vasculitis. Arch Dermatol. 1981;117:29-31.

25. Shaffer N, Kerdel FA. Nodular vasculitis (erythema induratum): treatment with auranofin. J Am Acad Dermatol. 1991;25(2, pt 2):426-429.

The absence of M tuberculosis organisms in skin lesions has led some to doubt the causal relationship between M tuberculosis and EIB.⁷ However, the advent of polymerase chain reaction (PCR) and specific DNA primers for M tuberculosis has allowed for the detection of M tuberculosis DNA in biopsy specimens, which has further established the relationship between tuberculosis and EIB.⁵ Some authors have suggested that the absence of mycobacteria in EIB and other tuberculid lesions may be due to small numbers of bacilli in the lesions or early destruction of mycobacteria organisms before biopsy.^8,9 These authors consider cutaneous tuberculosis and tuberculids as diseases on the same spectrum, with tuberculids representing one extreme in which there are few mycobacteria organisms present in the lesions.

Presentation

Erythema induratum commonly affects middle-aged women and presents with recurrent crops of tender nodules on the lower extremities.^10-13 Nodules often are most commonly found on the lower calves but also can present on the arms, thighs, feet, or buttocks.¹⁰ Our patient’s presentation was atypical in that lesions were distributed on the pretibial area of the legs and dorsal aspect of the feet. Obesity and venous insufficiency of the lower extremities are believed to be predisposing factors to the development of EIB nodules.² The nodules develop over several weeks and heal over several months with possible ulceration and hyperpigmented scarring.^10,11 Ulcerated nodules often are irregular and shallow with an overlying crust and a bluish border.^11,13 Nodules often are precipitated by cold weather or venostasis.^1,11,12

Silva et al¹⁴ reported a case of EIB on the lower legs associated with a burning sensation on the feet and paresthesia; all known causes of peripheral neuropathy were excluded by a comprehensive laboratory workup. The burning sensation on the feet resolved after several weeks of antituberculosis therapy. Our patient also presented with a burning sensation on the feet that remarkably improved after 6 months of antituberculosis therapy. Peripheral neuropathy could have been a consequence of diabetes mellitus in our patient, though neuronal damage also could be a consequence of hypersensitivity to tuberculosis antigens. Silva et al¹⁴ proposed that macrophages activated by M tuberculosis antigens produce lytic enzymes that can cause tissue necrosis and nerve damage if released into surrounding tissue.

Diagnosis

The diagnosis of EIB is made based on clinical presentation, evidence of prior or current tuberculosis infection, histopathologic findings, and response to antituberculosis therapy.¹⁵ Evidence of active or latent tuberculosis infection typically is gathered by patient history, chest radiograph, tuberculin skin tests, interferon-releasing assays, and PCR of skin biopsies. Tuberculin skin tests in patients with EIB result in reactive induration that is typically more than 20 mm.⁸ In vitro T-lymphocyte proliferation assays in response to PPD have further supported the suggestion that there is a markedly enhanced T-lymphocyte response to M tuberculosis antigens in patients with EIB.¹⁶

IFN-γ release assays have provided useful methods for the detection of latent tuberculosis infection.¹⁷ The IGRA is effective when the tuberculin skin test yields a suspected false-negative or in the context of prior bacille Calmette-Guérin vaccination.¹⁷ IFN-γ release assays also may be preferred to tuberculin skin tests because it provides less discomfort to the patient in the event of a positive hypersensitive reaction to the PPD.

Before the advent of IGRAs, PCR was used to detect M tuberculosis DNA in skin biopsies and to confirm the diagnosis of EIB. Some researchers believe PCR can be an important tool for confirming a diagnosis of EIB, especially in cases and countries where results from the Mantoux test do not have great value.^15,18 A PCR assay for detecting  M tuberculosis DNA in blood and urine samples also was found helpful in confirming a diagnosis of EIB when skin biopsies were unavailable.^8,19 However, PCR has been shown to have low sensitivity for the diagnosis of EIB because of its ability to detect M tuberculosis DNA ranging from  0% to 77% of skin biopsy specimens.^20,21 Therefore, a negative PCR for the detection of M tuberculosis DNA in nodules does not exclude a diagnosis of erythema induratum.

Treatment

The mainstay of EIB treatment is a multidrug antituberculosis regimen.^5,8,10-12 Our patient was successfully treated with rifampin and isoniazid and a repeat IGRA was used as a laboratory marker of response to therapy. Single-drug therapy with isoniazid has been shown to result in greater likelihood of EIB relapse in comparison to multidrug regimens.²² Other treatments include potassium iodide and gold, but they are not well-studied.^23-25 Treatment of venous insufficiency with bed rest and nonsteroidal anti-inflammatory drugs for pain also may be helpful.² In cases of nodular vasulitis that are not associated with tuberculosis infection, treatment should be targeted at the underlying cause of the immune response. For example, a case of nodular vasculitis associated with hepatitis C virus did not respond to antituberculosis multidrug therapy, but skin lesions did improve with pegylated interferon and ribavirin.⁴