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Background
Erythema induratum is a chronic, recurring panniculitis that is found predominantly on the legs of women with tuberculin hypersensitivity. Recent molecular studies, predominately using polymerase chain reaction, have isolated Mycobacterium tuberculosis DNA in many cases. It is currently believed that this disease represents a tuberculid, or hypersenstivity reaction to a M. tuberculosis infection.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Erythema induratum of Bazin, Nodular vasculitis INCIDENCE/
PREVALENCEAGE SEX GEOGRAPHY ENGLAND
- Cutaneous tuberculosis in Blackburn district (U.K.): a 15-year prospective series, 1981-95.
Yates VM, Ormerod LP.
Department of Dermatology, Blackburn Royal Infirmary, Lancs, UK.
Br J Dermatol. 1997 Apr;136(4):483-9. Abstract quote
Data collected prospectively on all 1065 cases of tuberculosis occurring in the Blackburn district, U.K. (population 265,000), over a 15-year period have been analysed, and from these 47 cases of cutaneous tuberculosis have been identified.
The most common form was scrofuloderma, skin involvement with adjacent structural disease, of which there were 26 cases (55.3%). There was no ethnic bias in this group. The eight white patients with scrofuloderma were of average age 66 years, and are thought to represent reactivation disease. Six patients (12.8%) had lupus vulgaris, four (8.5%) had metastatic tuberculosis and 10 (21.3%) were diagnosed as having one of the tuberculides, of which Bazin's disease (erythema induratum) was the most common. In addition, one patient (2.2%) had orificial tuberculosis. In contrast to scrofuloderma, all other forms of cutaneous tuberculosis occurred almost exclusively in patients from the Indian Subcontinent (ISC).
The high incidence of tuberculosis in Blackburn is mainly linked to its significant proportion of residents of ISC ethnic origin. There were no cases of HIV infection coexisting with either cutaneous or other forms of tuberculosis. Recommendations for the treatment of cutaneous tuberculosis are made.EPIDEMIOLOGIC ASSOCIATIONS
DISEASE ASSOCIATIONS CHARACTERIZATION TUBERCULOSIS
- Erythema induratum of Bazin and renal tuberculosis: report of an association.
Daher Ede F, Silva Junior GB, Pinheiro HC, Oliveira TR, Vilar Mdo L, Alcantara KJ.
Servicos de Dermatologia e Nefrologia, Hospital Universitario Walter Cantidio, Departamento de Medicina Clinica, Faculdade de Medicina, Universidade Federal do Ceara, Fortaleza, CE, Brazil.
Rev Inst Med Trop Sao Paulo. 2004 Sep-Oct;46(5):295-8. Epub 2004 Oct 22. Abstract quote
Erythema induratum of Bazin is a disease that usually affects women, in whom erythematous subcutaneous nodules and plaques appear on the posterior part of the lower extremities, some of which ulcerate. In many countries, tuberculosis is still the main etiologic factor.
We report a case of a 40-year-old woman who presented a course of protracted and recurrent episodes over five years of cutaneous lesions on her legs. These tend to involute, but new crops appear at irregular intervals. It was painful, erythematous-violaceous nodules, some of which drained a reddish secretion.
The histopathologic features of the lesions demonstrated inflammatory infiltration, with predominance of neutrophils in dermis and hypodermis, necrotizing vasculitis in the arterioles and septal fibrosis. There was no granuloma. The Ziehl-Neelsen stain did not revealed acid-fast bacilli, and the culture of biopsy specimen was negative. The tuberculin skin test was strongly positive (17 mm). The chest X-ray was normal. Few months later she presented adynamia and urinary complaints, such as polacyuria and dysuria. It has been done an urynalysis, which demonstrated acid pH urine, sterile pyuria and microscopic hematuria. It was then raised the diagnostic hypothesis of renal tuberculosis. The urine culture for M. tuberculosis was positive in two out of ten samples. The treatment was instituted with rifampin, isoniazid and pyrazinamide, with complete regression.
This case illustrates a clear association between erythema induratum and renal tuberculosis, demonstrated by the remission of the cutaneous lesions after the treatment of the renal tuberculosis.
- Erythema induratum associated with tuberculous lymphadenitis: analysis of a case using polymerase chain reactions with different primer pairs to differentiate bacille Calmette-Guerin (BCG) from virulent strains of Mycobacterium tuberculosis complex.
Wang TC, Tzen CY, Su HY.
Department of Dermatology and Department of Pathology, Mackay Memorial Hospital, 92, Sec 2, Chun-shan N Rd, Taipei 10449, Taiwan.
J Dermatol. 2000 Nov;27(11):717-23. Abstract quote
We retrospectively analyzed a bacille Calmette-Guerin (BCG) vaccinated female patient who developed erythema induratum in association with tuberculous lymphadenitis. The polymerase chain reaction (PCR) with two pairs of primers was performed. Only one pair was able to detect the myocobacterial DNA from the paraffin-embedded specimen of the erythema induratum (EI) lesion. However, both pairs showed positive results with the tuberculous lymphadenitis specimen. Sequence analysis of the PCR products excluded the possibility of BCG as the potential pathogen.
Both lesions responded favorably to antituberculous therapy. Our study attests to the tuberculous nature of EI and demonstrates that BCG vaccination per se does not induce the lesion or interfere with the PCR result.
Finally, using at least two pairs of primers targeting different genomic segments and possessing species-identification capability may raise the detection rates and solve some controversies about the nature of tuberculids.
PATHOGENESIS CHARACTERIZATION MYCOBACTERIUM
- Mycobacteria other than Mycobacterium tuberculosis are not present in erythema induratum/nodular vasculitis: a case series and literature review of the clinical and histologic findings.
Bayer-Garner IB, Cox MD, Scott MA, Smoller BR.
Marshfield Clinic, Marshfield, WI, USA.
J Cutan Pathol. 2005 Mar;32(3):220-6. Abstract quote
Erythema induratum (EI)/nodular vasculitis (NV) is characterized by recurrent crops of tender oedematous nodules on the lower legs. A lobular panniculitis with granulomatous inflammation, vasculitis, focal necrosis and septal fibrosis is present. Mycobacterium tuberculosis DNA has been detected in some lesions by means of polymerase chain reaction (PCR).
Ten cases of EI/NV were found. H&E slides were reviewed. PCR assays for M. tuberculosis and mycobacteria other than M. tuberculosis (MOTT) were performed. PCR did not reveal M. tuberculosis (0%) or MOTT (0%) DNA, with positive controls, indicating the reliability of the assays. Among the MOTT, cutaneous infections are most commonly caused by M. marinum. Subcutaneous tuberculoid granulomas may be seen with M. kansasii, M. marinum, M. scrofulaceum and M. avium complex. M. gordonae, M. szulgai and M. malmoense rarely cause cutaneous infections. M. simiae, M. gastri and M. asiaticum are probably not cutaneous pathogens. M. tuberculosis and MOTT DNA was not found in EI/NV. EI/NV has diverse aetiologies with varying pathogeneses leading to similar histologic changes.
The cases analysed may not have had an infectious aetiology. However, in EI/NV, performance of PCR for MOTT as well as M. tuberculosis complex may still be beneficial, particularly in cases from immunocompromised hosts.
- Erythema induratum: a clinicopathologic and polymerase chain reaction study.
Chen YH, Yan JJ, Chao SC, Lee JY.
Department of Dermatology, National Cheng-Kung University Hospital, 138 Sheng-Li Road, Tainan, Taiwan.
J Formos Med Assoc. 2001 Apr;100(4):244-9. Abstract quote
BACKGROUND: In Taiwan, cutaneous lesions with granulomatous lobular panniculitis, with or without vasculitis, are usually diagnosed as erythema induratum (EI), a common form of tuberculid associated with tuberculosis. However, there has been no study to elucidate the extent of this association in Taiwan. The aim of this study was to document the spectrum of the pathologic findings in EI and its association with Mycobacterium tuberculosis.
METHODS: The diagnostic/inclusion criteria for EI were recurrent tender subcutaneous nodules on the legs, histopathologic findings of granulomatous lobular or septolobular panniculitis plus necrosis or vasculitis, and positive response to antituberculosis therapy. The clinicopathologic findings in the 12 cases that fulfilled these criteria were analyzed, and nested polymerase chain reaction (PCR) was used to identify M. tuberculosis complex DNA from formalin-fixed, paraffin-embedded sections.
RESULTS: Eleven women and one man were included in the study, ranging from 18 to 70 years old (mean, 40.6 yr). The duration of the disease ranged from 10 days to 10 years (mean, 2.1 yr). Histopathology revealed granulomatous panniculitis; a diffuse lobular pattern was observed in nine cases and a focal lobular/septolobular pattern in three. Vasculitis was found in nine cases, four affecting an artery or vein, with three occurring in the patients with focal panniculitis. Ten cases showed various degrees of caseous necrosis. Eosinophils or focal eosinophilia were fairly common (10 patients). From PCR, nine patients were positive for M. tuberculosis complex DNA.
CONCLUSIONS: Type III and IV hypersensitivity reactions to M. tuberculosis complex were involved in the pathogenesis of EI. Our results suggest that approximately half of the cases with pathologic findings consistent with EI or nodular vasculitis in Taiwan are associated with M. tuberculosis.
- Erythema induratum of Bazin. A clinicopathological study of 20 cases and detection of Mycobacterium tuberculosis DNA in skin lesions by polymerase chain reaction.
Schneider JW, Jordaan HF, Geiger DH, Victor T, Van Helden PD, Rossouw DJ.
Department of Anatomical Pathology, Faculty of Medicine, University of Stellenbosch, Tygerberg, Republic of South Africa.
Am J Dermatopathol. 1995 Aug;17(4):350-6. Abstract quote
Erythema induratum of Bazin (EIB) is a chronic, recurring panniculitis that is found predominantly on the legs of women with tuberculin hypersensitivity. A causal relationship between EIB and Mycobacterium tuberculosis remains elusive because of the absence of demonstrable organisms in skin lesions. We reviewed the clinicopathological features of 20 patients (all women) with positive Mantoux tests (1:10,000 dilution) and characteristic skin lesions of EIB that cleared up with combined antituberculous treatment. Histological examination of skin lesions confirmed panniculitis with varying combinations of granulomatous inflammation, primary vasculitis, and necrosis. Sections from 20 formalin-fixed, paraffin-embedded skin biopsies obtained from the 20 patients were submitted for polymerase chain reaction (PCR) using oligonucleotide primers for the detection of a 123-bp DNA fragment specific for the M. tuberculosis complex. M. tuberculosis DNA was identified in five of the 20 biopsies. Meticulous care was taken to prevent contamination as a source of false-positive results. Mycobacterial DNA was absent in all negative controls and in normal skin biopsies from purified protein derivative-positive patients with and without EIB. These results provide direct evidence that mycobacterial components are present in EIB lesions and strongly suggest that M. tuberculosis is involved in the pathogenesis of EIB.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS PCR
- Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids.
Tan SH, Tan BH, Goh CL, Tan KC, Tan MF, Ng WC, Tan WC.
Institute of Dermatology, National Skin Centre, and Department of Medicine, National University Hospital, Singapore.
Int J Dermatol. 1999 Feb;38(2):122-7. Abstract quote
BACKGROUND:The objective of this study was to explore the role of the polymerase chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy specimens.
METHODS AND RESULTS: A wide range of clinical specimens representing different forms of cutaneous tuberculosis and so-called tuberculids were studied. A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium tuberculosis complex was used. The specimens were categorized as follows. 1 Acid-fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who were immunocompromised). PCR was positive in five specimens. Of these, one specimen was culture positive and three specimens were culture negative. 2 AFB negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six specimens). PCR was negative in all specimens. 3 Tuberculids.' (a) erythema induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two specimens); (c) erythema nodosum (20 specimens). PCR was negative in all specimens.
CONCLUSIONS: The role of PCR in clinical dermatologic practice, at this stage, may be in differentiating between cutaneous tuberculosis and atypical mycobacterial infections in the context of an immunocompromised patient where AFB can be demonstrated on biopsy and cultures may be negative. In this clinical situation, PCR allows the prompt diagnosis and early institution of appropriate therapy. We have not found PCR to be a useful complement to the clinical and histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL
- Erythema nodosum.
Requena L, Requena C.
Department of Dermatology, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.
Dermatol Online J. 2002 Jun;8(1):4. Abstract quote
Erythema nodosum is the most frequent clinico-pathological variant of the panniculitides. The disorder is a cutaneous reaction consisting of inflammatory, tender, nodular lesions, usually located on the anterior aspects of the lower extremities. The process may be associated with a wide variety of diseases, being infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies the most common associated conditions.
The typical eruption consists of a sudden onset of symmetrical, tender, erythematous, warm nodules and raised plaques usually located on the shins, ankles and knees. Often the lesions are bilaterally distributed. At first, the nodules show a bright red color, but within a few days they become livid red or purplish, and finally they exhibit a yellow or greenish appearance taking on the look of a deep bruise.
Ulceration is never seen and the nodules heal without atrophy or scarring. Some clinical variants of erythema nodosum have been described under different names, including erythema nodosum migrans, subacute nodular migratory panniculitis, and chronic erythema nodosum, but probably they are just clinical variants which may all be included within the spectrum of erythema nodosum.
Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The septa of subcutaneous fat are always thickened and variously infiltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. In early lesions edema, hemorrhage, and neutrophils are responsible for the septal thickening, whereas fibrosis, periseptal granulation tissue, lymphocytes, and multinucleated giant cells are the main findings in late stage lesions of erythema nodosum.
A histopathologic hallmark of erythema nodosum is the presence of the so-called Miescher's radial granulomas, which consist of small, well-defined nodular aggregations of small histiocytes arranged radially around a central cleft of variable shape. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified. Usually, nodules of erythema nodosum regress spontaneously within a few weeks, and bed rest is often sufficient treatment.
Aspirin, nonsteroidal anti-inflammatory drugs, such as oxyphenbutazone, indomethacin or naproxen, and potassium iodide may be helpful drugs to enhance analgesia and resolution. Systemic corticosteroids are rarely indicated in erythema nodosum and before these drugs are administered an underlying infection should be ruled out.VARIANTS
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
The histopathologic spectrum of erythema induratum of Bazin.
Schneider JW, Jordaan HF.
Department of Anatomical Pathology, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
Am J Dermatopathol. 1997 Aug;19(4):323-33. Abstract quote
Erythema induratum of Bazin is a tuberculid that is strongly associated with tuberculosis. Clinically, erythema induratum of Bazin show recurrent tender subcutaneous nodules that occur mainly on the calves of women with tuberculin hypersensitivity. Previous studies have not documented the histopathologic spectrum of erythema induratum of Bazin in detail.
We identified two major histopathologic groups in 19 of 20 skin biopsies obtained from 20 patients with well-documented erythema induratum of Bazin. Six cases (group I) showed focal septolobular panniculitis in close association with a single muscular artery or small vessel with primary neutrophilic vasculitis. Thirteen cases (group II) revealed diffuse septolobular panniculitis with primary neutrophilic vasculitis of either large or smaller vessels. Both groups showed varying combinations and degrees of acute and chronic inflammation, coagulative and caseation-like necrosis, and granulomatous inflammation. Poorly developed granulomas predominated, but mixed, palisading, and lipophagic granulomas also occurred. Inflammation and necrosis were more extensive in group II. Erythema induratum of Bazin may show predominantly acute suppurative or granulomatous panniculitis. Immunostaining showed S100+ antigen-presenting cells, macrophages, and T-lymphocytes. B-lymphocytes were rare.
The presence of primary vasculitis and granulomas suggests that types III and IV hypersensitivity reactions play a role in the pathogenesis or erythema induratum of Bazin. The latter remains a clinicopathologic diagnosis, but awareness of the heterogeneous histopathologic spectrum of EIB will ensure a timely diagnosis and institution of antituberculous treatment.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ELECTRON MICROSCOPY
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES GENERAL
- Inflammatory nodules of the lower legs: a clinical and histological analysis of 134 cases in Korea.
Cho KH, Kim YG, Yang SG, Lee DY, Chung JH.
Department of Dermatology, Seoul National University College of Medicine, Korea.
J Dermatol. 1997 Aug;24(8):522-9. Abstract quote
We analysed 134 Korean cases with inflammatory nodules of the lower legs on the basis of clinicopathological findings, responsiveness to various therapeutic agents, and clinical course.
There were 53 cases of erythema induratum (EI), 18 of erythema nodosum (EN), 40 of EN-like lesions of Behcet's disease, 15 of other entities, including superficial migratory thrombophlebitis, cutaneous periarteritis nodosa, sarcoidosis, malignant lymphoma, Churg-Strauss syndrome, and parasitosis, and eight unclassified cases. The unclassified group was composed of a spectrum of diseases with clinicopathologic features ranging between those typical of EN and EI.
The present study revealed that the profiles of diseases featuring inflammatory nodules of the lower legs in Korea differed from those found in other areas. These geographic and demographic differences should be kept in mind when managing a patient with inflammatory nodules of the lower legs.
- Nodules on the legs. A clinical, histological and immunohistological study of 82 patients representing different types of nodular panniculitis.
Niemi KM, Forstrom L, Hannuksela M, Mustakallio KK, Salo OP.
Acta Derm Venereol. 1977;57(2):145-54. Abstract quote
Eighty-two cases of nodular panniculitis of the legs were examined clinically, histologically and immunohistologically. Clinically the cases could be divided into four groups: typical erythema nodosum (ENty) (35 cases), erythema nodosum migrans (ENmi) (11 cases), erythema induratum (EI) (11 cases) and the remaining 25 cases not consistent with the others as "non-definite panniculitis" (NDP).
The main histological categories were septal panniculitis and lobular panniculitis, the former including erythema nodosum, both typical and migrans, the latter EI and NDP. Lobular panniculitis was divided into three subgroups in which the most prominent histological features were epithelioid cell granuloma, vasculitis and palissading granuloma, respectively. Immunoglobulins in the vessel walls were found in 5 of the 46 cases of erythema nodosum, in 19 of the 36 EI and NDP cases and, in the histological groups in 4 of the 43 cases of septal panniculitis and in 19 of the 35 cases of lobular panniculitis, respectively. Fibrin was found in the walls of the papillary capillaries and deep dermal vessels in the majority of cases of lobular panniculitis.
In EI and NDP the follow-up time was 40 months, on average. Twenty-two patients were treated with antituberculous drugs, 15 became symptomless, as did 5 of the 12 patients who were not treated at all.
PROGNOSIS CHARACTERIZATION
TREATMENT CHARACTERIZATION GENERAL ANTIBIOTICS
- Erythema induratum of Bazin and Poncet's disease -- successful treatment with antitubercular drugs.
Heinemann C, Kaatz M, Elsner P.
Department of Dermatology and Dermatological Allergology, University-Hospitals of the Friedrich Schiller University Jena, Erfurterstr. 35, 07740 Jena, Germany.
J Eur Acad Dermatol Venereol. 2003 May;17(3):334-6. Abstract quote
Erythema induratum of Bazin (EIB) is considered a tuberculide reaction and consists of recurrent painful nodules predominantly on the calves. Clinically it has common features with diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. Poncet's disease is a reactive arthritis that may accompany tuberculosis.
We report a case of a young woman in which the simultaneous occurrence of erythema induratum of Bazin and Poncet's disease led to a clinical picture very similar to Lofgren's syndrome. The final diagnosis was obtained by polymerase chain reaction detection of mycobacterial DNA in a skin biopsy. A systemic therapy with tuberculostatic drugs led to the disappearance of symptoms.
The presented case shows the usefulness of polymerase chain reaction diagnostics in EIB patients without other clinical signs of tuberculosis and a confusing combination of symptoms, and further confirms the presence of mycobacterial DNA in EIB lesions.Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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