Case for Diagnosis DOI: 10.1111/ddg.12579
Erythematous nodule on the earlobe in a patient from Iraq
History A 41-year-old female patient presented with a 10-year history of an asymptomatic, slowly growing nodule on her earlobe. The patient was originally from Iraq and had lived in Germany for eight years. Her past medical history was unremarkable regarding preexisting conditions. The patient denied general symptoms such as fever, weight loss, cough, expectoration, and dyspnea.
Clinical findings The physical exam showed an erythematous, partly scaly nodule on the patient’s right earlobe, measuring 2.5 × 1.5 cm in size (Figure 1). The lymph nodes were unremarkable on palpation. There were no other pathological findings.
Histology Diagnostic excision revealed tuberculoid granulomas without central necrosis, surrounded by an edematous inflammatory reaction with a predominantly lymphocytic infiltrate (Figure 2a, b). Polarized light microscopy showed no b irefringent material. PAS and Grocott staining yielded no fungal elements; Ziehl-Neelsen staining was negative for acid-fast bacilli.
Figure 1 Erythematous, partly scaly nodule on the right earlobe.
Figure 2 Hematoxylin-eosin (H&E) stained tissue. The overview (a) shows an edematous inflammatory reaction with tuberculous granulomas throughout the dermis. Higher magnification (b) reveals a dense predominantly lymphocytic infiltrate with some plasma cells and neutrophilic granulocytes as well as multinucleated giant cells within the granulomas. There are no central necroses (original magnification × 40 (a) and x 100 (b)).
Your diagnosis? …
588
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
Case for Diagnosis Diagnosis: Lupus vulgaris
Further diagnostic workup In view of the history, clinical picture, and histological findings, we proposed a working diagnosis of lupus vulgaris. The diagnosis was subsequently confirmed by culture isolation of Mycobacterium tuberculosis and a positive QuantiFERON-TB Gold (QFT®) test. Antimicrobial susceptibility testing showed sensitivity to isoniazid, rifampicin, pyrazinamide, and ethambutol. Cultures for bacteria, fungi and ubiquitous mycobacteria, as well as nucleic acid amplification of atypical mycobacteria, were all negative. Antibodies against Leishmania were not detectable, the angiotensin-converting enzyme levels were within normal limits, and the Treponema pallidum particle agglutination (TPPA) test was negative. Chest X-ray (in two planes) was unremarkable. Clinically, there was no evidence of meningeal or cerebral tuberculosis or other organ manifestations. The patient decided not to undergo further diagnostic workup, which would have been therapeutically inconsequential anyway due to the presence of paucibacillary extrapulmonary tuberculosis with sensitivity to all antituberculosis drugs tested. Contact investigation revealed no other cases of tuberculosis.
Therapy and clinical course The patient’s CBC as well as liver and kidney parameters were within normal limits, and hepatitis serology was negative. In cooperation with the Department of Infectious Diseases, we therefore initiated weight-adapted tuberculostatic triple therapy with isoniazid plus pyridoxine 300 mg (5 mg/kg BW once daily), rifampicin 600 mg (10 mg/kg BW once daily) and pyrazinamide 1,500 mg (25 mg/kg BW once daily.). One month after the start of therapy, the lesion had almost completely healed. After two months, we switched the patient to a dual combination of isoniazid and rifampicin, which was to be continued for four months.
Discussion According to the World Health Organization, nearly nine million people annually contract tuberculosis, with roughly 85 % living in Africa, Southeast Asia, and the Western Pacific region. In Germany, the incidence is 5.2/100,000 per year, and in Iraq, our patient’s home country, 45/100,000. While the most commonly affected organ is the lung (pulmonary TB), about 10–20 % of patients have purely extrapulmonary
tuberculosis. Less than 2 % of all tuberculosis variants affect the skin, with lupus vulgaris being the most common cutaneous manifestation [1]. Lupus vulgaris is a form of postprimary tuberculosis associated with normergy. It is usually caused by Mycobacterium tuberculosis, which reaches the dermis either by exogenous inoculation or by dissemination from an affected internal organ through hematogenous or lymphogenous spread [2]. Up to 40 % of patients additionally present with tuberculous lymphadenitis, and 20 % with pulmonary or osseous tuberculosis [3]. Clinically, lupus vulgaris initially presents as a reddish-brown nodule that gradually evolves into an asymptomatic plaque with an atrophic surface [1, 4–7]. Verrucous, hypertrophic, ulcerative, necrotic, and vegetating forms have also been described. Diascopy shows an apple jelly-like infiltrate [1, 4]. Depending on specific findings, differential diagnoses may include psoriasis, tinea, sarcoidosis, atypical mycobacteriosis, leprosy, leishmaniasis, cutaneous lymphoma, and epithelial tumors [5–7]. The histopathology of lupus vulgaris is varied. While tuberculoid granulomas – epithelioid granulomas surrounded by a dense infiltrate of lymphocytes and plasma cells – are characteristic, they are not specific. Central necrosis (caseation) is a rare finding. Based on the paucity of pathogens, acid-fast staining (Ziehl-Neelsen stain) usually does not reveal any acid-fast bacilli, especially in the absence of central necrosis. To confirm the diagnosis, the QuantiFERON-TB Gold (QFT®) test should be performed, which indirectly detects tuberculosis pathogens through an interferon gamma release assay. The gold standard is the isolation of M. tuberculosis by culture, which is also indispensable for antibiotic resistance testing. In addition, biopsy material can be used in PCR, which has the advantage of providing rapid results. Organ involvement should always be ruled out [3, 8]. The standard treatment for extrapulmonary tuberculosis consists of a quadruple combination for two months, followed by a dual combination of isoniazid and rifampicin for four months [9]. In case of low bacterial load and evidence of sensitivity to isoniazid, rifampicin, and pyrazinamide, the fourth drug – ethambutol – may not be necessary in the initial phase [9]. A clinical response can be expected after four to six weeks [10]. Due to its paucibacillary nature, lupus vulgaris is diagnostically challenging and may remain undiagnosed for many years [5, 6]. Our case report shows that it is important to consider this rare disease in the differential diagnosis, especially in patients from high-risk regions. Conflict of interest None.
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
589
Case for Diagnosis
Miriam Linke1, Cyrill Géraud1, Faisal Tobeigei1, Roger Vogelmann2, Alexander Marx3, Sergij Goerdt1, Wiebke K. Peitsch1 (1) Department of Dermatology, Venereology and Allergology, University Hospital Mannheim, Heidelberg University, Mannheim (2) 2nd Department of Medicine, University Hospital Mannheim, Heidelberg University, Mannheim (3) Institute of Pathology, University Hospital Mannheim, Heidelberg University, Mannheim
Correspondence to Prof. Wiebke K. Ludwig-Peitsch, M.D. Department of Dermatology, Venereology and Allergology University Hospital Mannheim Heidelberg University Theodor-Kutzer-Ufer 1–3 68135 Mannheim Germany E-mail: [email protected]
590
References 1
Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol 2007; 25: 173–80. 2 Santos JB, Figueiredo AR, Ferraz CE et al. Cutaneous tuberculosis: epidemiologic, etiopathogenic and clinical aspects – part I. An Bras Dermatol 2014; 89: 219–28. 3 Almaguer-Chávez J, Ocampo-Candiani J, Rendón A. Current panorama in the diagnosis of cutaneous tuberculosis. Actas Dermosifiliogr 2009; 100: 562–70. 4 Fariña MC, Gegundez MI, Piqué E et al. Cutaneous tuberculosis: a clinical, histopathologic, and bacteriologic study. J Am Acad Dermatol 1995; 33: 433–40. 5 Sammain A, Jocher A, Bruckner-Tuderman L, Schempp CM. Lupus vulgaris – a case diagnosed more than 20 years after onset. J Dtsch Dermatol Ges 2006; 4: 958–60. 6 Stoevesandt J, Kurzai O, Bröcker EB, Hamm H. Persistent reddish-brown plaque on the occiput of a 62-year-old patient. J Dtsch Dermatol Ges 2007; 5: 55–7. 7 Barbagallo J, Tager P, Ingleton R et al. Cutaneous tuberculosis: diagnosis and treatment. Am J Clin Dermatol 2002; 3: 319–28. 8 dos Santos JB, Figueiredo AR, Ferraz CE et al. Cutaneous tuberculosis: diagnosis, histopathology and treatment – part II. An Bras Dermatol 2014; 89: 545–55. 9 Schaberg T, Forssbohm M, Hauer B et al. Richtlinien zur medikamentösen Behandlung der Tuberkulose im Erwachsenen- und Kindesalter. Pneumologie 2001; 55: 494–511. 10 Ramam M, Mittal R, Ramesh V. How soon does cutaneous tuberculosis respond to treatment? Implications for a therapeutic test of diagnosis. Int J Dermatol 2005; 44: 121–4.
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
Erythematous nodule on the earlobe in a patient from Iraq
History A 41-year-old female patient presented with a 10-year history of an asymptomatic, slowly growing nodule on her earlobe. The patient was originally from Iraq and had lived in Germany for eight years. Her past medical history was unremarkable regarding preexisting conditions. The patient denied general symptoms such as fever, weight loss, cough, expectoration, and dyspnea.
Clinical findings The physical exam showed an erythematous, partly scaly nodule on the patient’s right earlobe, measuring 2.5 × 1.5 cm in size (Figure 1). The lymph nodes were unremarkable on palpation. There were no other pathological findings.
Histology Diagnostic excision revealed tuberculoid granulomas without central necrosis, surrounded by an edematous inflammatory reaction with a predominantly lymphocytic infiltrate (Figure 2a, b). Polarized light microscopy showed no b irefringent material. PAS and Grocott staining yielded no fungal elements; Ziehl-Neelsen staining was negative for acid-fast bacilli.
Figure 1 Erythematous, partly scaly nodule on the right earlobe.
Figure 2 Hematoxylin-eosin (H&E) stained tissue. The overview (a) shows an edematous inflammatory reaction with tuberculous granulomas throughout the dermis. Higher magnification (b) reveals a dense predominantly lymphocytic infiltrate with some plasma cells and neutrophilic granulocytes as well as multinucleated giant cells within the granulomas. There are no central necroses (original magnification × 40 (a) and x 100 (b)).
Your diagnosis? …
588
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
Case for Diagnosis Diagnosis: Lupus vulgaris
Further diagnostic workup In view of the history, clinical picture, and histological findings, we proposed a working diagnosis of lupus vulgaris. The diagnosis was subsequently confirmed by culture isolation of Mycobacterium tuberculosis and a positive QuantiFERON-TB Gold (QFT®) test. Antimicrobial susceptibility testing showed sensitivity to isoniazid, rifampicin, pyrazinamide, and ethambutol. Cultures for bacteria, fungi and ubiquitous mycobacteria, as well as nucleic acid amplification of atypical mycobacteria, were all negative. Antibodies against Leishmania were not detectable, the angiotensin-converting enzyme levels were within normal limits, and the Treponema pallidum particle agglutination (TPPA) test was negative. Chest X-ray (in two planes) was unremarkable. Clinically, there was no evidence of meningeal or cerebral tuberculosis or other organ manifestations. The patient decided not to undergo further diagnostic workup, which would have been therapeutically inconsequential anyway due to the presence of paucibacillary extrapulmonary tuberculosis with sensitivity to all antituberculosis drugs tested. Contact investigation revealed no other cases of tuberculosis.
Therapy and clinical course The patient’s CBC as well as liver and kidney parameters were within normal limits, and hepatitis serology was negative. In cooperation with the Department of Infectious Diseases, we therefore initiated weight-adapted tuberculostatic triple therapy with isoniazid plus pyridoxine 300 mg (5 mg/kg BW once daily), rifampicin 600 mg (10 mg/kg BW once daily) and pyrazinamide 1,500 mg (25 mg/kg BW once daily.). One month after the start of therapy, the lesion had almost completely healed. After two months, we switched the patient to a dual combination of isoniazid and rifampicin, which was to be continued for four months.
Discussion According to the World Health Organization, nearly nine million people annually contract tuberculosis, with roughly 85 % living in Africa, Southeast Asia, and the Western Pacific region. In Germany, the incidence is 5.2/100,000 per year, and in Iraq, our patient’s home country, 45/100,000. While the most commonly affected organ is the lung (pulmonary TB), about 10–20 % of patients have purely extrapulmonary
tuberculosis. Less than 2 % of all tuberculosis variants affect the skin, with lupus vulgaris being the most common cutaneous manifestation [1]. Lupus vulgaris is a form of postprimary tuberculosis associated with normergy. It is usually caused by Mycobacterium tuberculosis, which reaches the dermis either by exogenous inoculation or by dissemination from an affected internal organ through hematogenous or lymphogenous spread [2]. Up to 40 % of patients additionally present with tuberculous lymphadenitis, and 20 % with pulmonary or osseous tuberculosis [3]. Clinically, lupus vulgaris initially presents as a reddish-brown nodule that gradually evolves into an asymptomatic plaque with an atrophic surface [1, 4–7]. Verrucous, hypertrophic, ulcerative, necrotic, and vegetating forms have also been described. Diascopy shows an apple jelly-like infiltrate [1, 4]. Depending on specific findings, differential diagnoses may include psoriasis, tinea, sarcoidosis, atypical mycobacteriosis, leprosy, leishmaniasis, cutaneous lymphoma, and epithelial tumors [5–7]. The histopathology of lupus vulgaris is varied. While tuberculoid granulomas – epithelioid granulomas surrounded by a dense infiltrate of lymphocytes and plasma cells – are characteristic, they are not specific. Central necrosis (caseation) is a rare finding. Based on the paucity of pathogens, acid-fast staining (Ziehl-Neelsen stain) usually does not reveal any acid-fast bacilli, especially in the absence of central necrosis. To confirm the diagnosis, the QuantiFERON-TB Gold (QFT®) test should be performed, which indirectly detects tuberculosis pathogens through an interferon gamma release assay. The gold standard is the isolation of M. tuberculosis by culture, which is also indispensable for antibiotic resistance testing. In addition, biopsy material can be used in PCR, which has the advantage of providing rapid results. Organ involvement should always be ruled out [3, 8]. The standard treatment for extrapulmonary tuberculosis consists of a quadruple combination for two months, followed by a dual combination of isoniazid and rifampicin for four months [9]. In case of low bacterial load and evidence of sensitivity to isoniazid, rifampicin, and pyrazinamide, the fourth drug – ethambutol – may not be necessary in the initial phase [9]. A clinical response can be expected after four to six weeks [10]. Due to its paucibacillary nature, lupus vulgaris is diagnostically challenging and may remain undiagnosed for many years [5, 6]. Our case report shows that it is important to consider this rare disease in the differential diagnosis, especially in patients from high-risk regions. Conflict of interest None.
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
589
Case for Diagnosis
Miriam Linke1, Cyrill Géraud1, Faisal Tobeigei1, Roger Vogelmann2, Alexander Marx3, Sergij Goerdt1, Wiebke K. Peitsch1 (1) Department of Dermatology, Venereology and Allergology, University Hospital Mannheim, Heidelberg University, Mannheim (2) 2nd Department of Medicine, University Hospital Mannheim, Heidelberg University, Mannheim (3) Institute of Pathology, University Hospital Mannheim, Heidelberg University, Mannheim
Correspondence to Prof. Wiebke K. Ludwig-Peitsch, M.D. Department of Dermatology, Venereology and Allergology University Hospital Mannheim Heidelberg University Theodor-Kutzer-Ufer 1–3 68135 Mannheim Germany E-mail: [email protected]
590
References 1
Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol 2007; 25: 173–80. 2 Santos JB, Figueiredo AR, Ferraz CE et al. Cutaneous tuberculosis: epidemiologic, etiopathogenic and clinical aspects – part I. An Bras Dermatol 2014; 89: 219–28. 3 Almaguer-Chávez J, Ocampo-Candiani J, Rendón A. Current panorama in the diagnosis of cutaneous tuberculosis. Actas Dermosifiliogr 2009; 100: 562–70. 4 Fariña MC, Gegundez MI, Piqué E et al. Cutaneous tuberculosis: a clinical, histopathologic, and bacteriologic study. J Am Acad Dermatol 1995; 33: 433–40. 5 Sammain A, Jocher A, Bruckner-Tuderman L, Schempp CM. Lupus vulgaris – a case diagnosed more than 20 years after onset. J Dtsch Dermatol Ges 2006; 4: 958–60. 6 Stoevesandt J, Kurzai O, Bröcker EB, Hamm H. Persistent reddish-brown plaque on the occiput of a 62-year-old patient. J Dtsch Dermatol Ges 2007; 5: 55–7. 7 Barbagallo J, Tager P, Ingleton R et al. Cutaneous tuberculosis: diagnosis and treatment. Am J Clin Dermatol 2002; 3: 319–28. 8 dos Santos JB, Figueiredo AR, Ferraz CE et al. Cutaneous tuberculosis: diagnosis, histopathology and treatment – part II. An Bras Dermatol 2014; 89: 545–55. 9 Schaberg T, Forssbohm M, Hauer B et al. Richtlinien zur medikamentösen Behandlung der Tuberkulose im Erwachsenen- und Kindesalter. Pneumologie 2001; 55: 494–511. 10 Ramam M, Mittal R, Ramesh V. How soon does cutaneous tuberculosis respond to treatment? Implications for a therapeutic test of diagnosis. Int J Dermatol 2005; 44: 121–4.
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
