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Systemic necrotizing vasculitis induced by isoniazid
Cardiovascular Pathology 23 (2014) 181–182
Contents lists available at ScienceDirect
Cardiovascular Pathology
Images in Cardiovascular Pathology
Systemic necrotizing vasculitis induced by isoniazid Carmela D. Tan ⁎, Amber Smith, E. Rene Rodriguez Department of Anatomic Pathology, The Cleveland Clinic, 9500 Euclid Avenue L25, Cleveland, OH 44195, USA
a r t i c l e
i n f o
Article history: Received 2 January 2014 Accepted 3 January 2014
a b s t r a c t A rare fatal case of antineutrophil cytoplasmic antibody-positive vasculitis induced by isoniazid is described. © 2014 Elsevier Inc. All rights reserved.
Keywords: Isoniazid ANCA Vasculitis
A 59-year-old woman, Filipino immigrant, presented with fever, weight loss, and progressive upper and lower extremity weakness of 6week duration. She was started on isoniazid for latent tuberculosis treatment 4 months prior. Treatment was discontinued 2 weeks before admission. On examination, there was sensory loss and motor weakness of the distal extremities with absent reflexes. There were no skin lesions. She was found to have mild anemia (hemoglobin 9.5 g/dl, hematocrit 29.8%), leukocytosis (14.35 k/μl), eosinophilia (1.06 k/μl), elevated liver enzymes (aspartate aminotransferase 114 U/L, alanine aminotransferase 132 U/L, alkaline phosphatase 737 U/L), and renal insufficiency (blood urea nitrogen 48 mg/dl, creatinine 2.6 mg/dl). On the fifth hospital day, she complained of severe sudden-onset abdominal pain and then became unresponsive. Hemoperitoneum with possible bleeding from the left lobe of the liver was suspected on computed tomography scan supported by a marked drop in hemoglobin from 9.5 to 2.3 g/dl. An angiogram demonstrated multiple microaneurysms affecting the hepatic, pancreatic, superior mesenteric, and renal artery distributions (Fig. 1). Empiric embolization of the left hepatic artery was performed. Rheumatologic workup revealed positive indirect immunofluorescence and elevated titer of 86 U for antineutrophil cytoplasmic antibodies directed against myeloperoxidase (p-ANCA). Hepatitis virus serology panel, cryoglobulins, and autoantibodies were negative. The patient was started on high-dose steroid therapy and cyclophosphamide. Her status continued to deteriorate with renal failure and hypotension. She died on the eight hospital day. Autopsy revealed hemoperitoneum of 2 L secondary to a ruptured intraparenchymal hematoma of the left lobe of the liver (8×7×3.5 cm). The right liver lobe also contained a hematoma. Multiple hemorrhagic cystic lesions were grossly visible in the portal tracts of
Funding: The authors have no financial disclosures. The authors received no federal or private industry funding. ⁎ Corresponding author. Tel.: +1 216 444 9489; fax: +1 216 445 3707. E-mail address: [email protected] (C.D. Tan). 1054-8807/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.carpath.2014.01.002
the liver and the renal cortices (Fig. 2A). Microscopic examination showed necrotizing vasculitis of medium-sized and small muscular arteries that were noted in the liver, kidneys, heart, spleen, pancreas, gastrointestinal tract, mesentery, adrenal glands, and uterus (Fig. 2B). There was segmental involvement of the arteries that showed fibrinoid necrosis with mixed inflammatory cell infiltrates involving all layers of the vessel wall and aneurysm formation (Fig. 2C, D). The lesions were of the same age. There were no granulomas. There was no evidence of glomerulonephritis or pulmonary involvement. The main differential diagnosis in this case was polyarteritis nodosa. However, ANCA is typically absent in patients with polyarteritis nodosa [1]. On the other hand, several drugs are known to induce ANCA, most commonly against myeloperoxidase, although
Fig. 1. Visceral angiogram revealed multiple microaneurysms affecting both lobes of the liver.
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C.D. Tan et al. / Cardiovascular Pathology 23 (2014) 181–182
Fig. 2. A, The liver shows multiple dilated vessels in the portal tracts and parenchymal hemorrhage. B, Scanning photomicrograph shows dilated branches of the hepatic artery with intimal hyperplasia, fibrinoid necrosis, and dense inflammation (hematoxylin and eosin, 20×). C and D, A muscular type artery shows segmental involvement with transmural inflammation and disruption of the internal elastic lamina. The lumen contains gelfoam used for embolization (C—hematoxylin and eosin, 100×; D—Movat pentachrome, 100×).
rarely are associated with vasculitis [2]. The drug singularity and temporal association of onset of symptoms with exposure to isoniazid are most consistent with a drug-induced ANCA-positive vasculitis. Antituberculosis medications that have been associated with vasculitis are rifampin and pyrazinamide, while isoniazid is more commonly associated with drug-induced lupus [3]. However, it has been hypothesized that lupus and vasculitis induction may not be through two entirely different mechanisms in drug-induced syndromes [4]. In summary, we report a rare fatal case of systemic necrotizing vasculitis in a patient treated with isoniazid. Drugs should be included in the differential diagnosis of ANCA-associated vasculitides.
References [1] Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 Revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum 2013;65:1–11. [2] Csernok E, Lamprecht P, Gross W. Clinical and immunological features of druginduced and infection-induced proteinase 3-antineutrophil cytoplasmic antibodies and vasculitis. Curr Opin Rheumatol 2010;22:43–8. [3] Marzano AV, Vezzoli P, Crosti C. Drug-induced lupus: an update on its dermatologic aspects. Lupus 2009;18:935–40. [4] Wiik A. Drug-induced vasculitis. Curr Opin Rheumatol 2008;20:35–9.
Contents lists available at ScienceDirect
Cardiovascular Pathology
Images in Cardiovascular Pathology
Systemic necrotizing vasculitis induced by isoniazid Carmela D. Tan ⁎, Amber Smith, E. Rene Rodriguez Department of Anatomic Pathology, The Cleveland Clinic, 9500 Euclid Avenue L25, Cleveland, OH 44195, USA
a r t i c l e
i n f o
Article history: Received 2 January 2014 Accepted 3 January 2014
a b s t r a c t A rare fatal case of antineutrophil cytoplasmic antibody-positive vasculitis induced by isoniazid is described. © 2014 Elsevier Inc. All rights reserved.
Keywords: Isoniazid ANCA Vasculitis
A 59-year-old woman, Filipino immigrant, presented with fever, weight loss, and progressive upper and lower extremity weakness of 6week duration. She was started on isoniazid for latent tuberculosis treatment 4 months prior. Treatment was discontinued 2 weeks before admission. On examination, there was sensory loss and motor weakness of the distal extremities with absent reflexes. There were no skin lesions. She was found to have mild anemia (hemoglobin 9.5 g/dl, hematocrit 29.8%), leukocytosis (14.35 k/μl), eosinophilia (1.06 k/μl), elevated liver enzymes (aspartate aminotransferase 114 U/L, alanine aminotransferase 132 U/L, alkaline phosphatase 737 U/L), and renal insufficiency (blood urea nitrogen 48 mg/dl, creatinine 2.6 mg/dl). On the fifth hospital day, she complained of severe sudden-onset abdominal pain and then became unresponsive. Hemoperitoneum with possible bleeding from the left lobe of the liver was suspected on computed tomography scan supported by a marked drop in hemoglobin from 9.5 to 2.3 g/dl. An angiogram demonstrated multiple microaneurysms affecting the hepatic, pancreatic, superior mesenteric, and renal artery distributions (Fig. 1). Empiric embolization of the left hepatic artery was performed. Rheumatologic workup revealed positive indirect immunofluorescence and elevated titer of 86 U for antineutrophil cytoplasmic antibodies directed against myeloperoxidase (p-ANCA). Hepatitis virus serology panel, cryoglobulins, and autoantibodies were negative. The patient was started on high-dose steroid therapy and cyclophosphamide. Her status continued to deteriorate with renal failure and hypotension. She died on the eight hospital day. Autopsy revealed hemoperitoneum of 2 L secondary to a ruptured intraparenchymal hematoma of the left lobe of the liver (8×7×3.5 cm). The right liver lobe also contained a hematoma. Multiple hemorrhagic cystic lesions were grossly visible in the portal tracts of
Funding: The authors have no financial disclosures. The authors received no federal or private industry funding. ⁎ Corresponding author. Tel.: +1 216 444 9489; fax: +1 216 445 3707. E-mail address: [email protected] (C.D. Tan). 1054-8807/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.carpath.2014.01.002
the liver and the renal cortices (Fig. 2A). Microscopic examination showed necrotizing vasculitis of medium-sized and small muscular arteries that were noted in the liver, kidneys, heart, spleen, pancreas, gastrointestinal tract, mesentery, adrenal glands, and uterus (Fig. 2B). There was segmental involvement of the arteries that showed fibrinoid necrosis with mixed inflammatory cell infiltrates involving all layers of the vessel wall and aneurysm formation (Fig. 2C, D). The lesions were of the same age. There were no granulomas. There was no evidence of glomerulonephritis or pulmonary involvement. The main differential diagnosis in this case was polyarteritis nodosa. However, ANCA is typically absent in patients with polyarteritis nodosa [1]. On the other hand, several drugs are known to induce ANCA, most commonly against myeloperoxidase, although
Fig. 1. Visceral angiogram revealed multiple microaneurysms affecting both lobes of the liver.
182
C.D. Tan et al. / Cardiovascular Pathology 23 (2014) 181–182
Fig. 2. A, The liver shows multiple dilated vessels in the portal tracts and parenchymal hemorrhage. B, Scanning photomicrograph shows dilated branches of the hepatic artery with intimal hyperplasia, fibrinoid necrosis, and dense inflammation (hematoxylin and eosin, 20×). C and D, A muscular type artery shows segmental involvement with transmural inflammation and disruption of the internal elastic lamina. The lumen contains gelfoam used for embolization (C—hematoxylin and eosin, 100×; D—Movat pentachrome, 100×).
rarely are associated with vasculitis [2]. The drug singularity and temporal association of onset of symptoms with exposure to isoniazid are most consistent with a drug-induced ANCA-positive vasculitis. Antituberculosis medications that have been associated with vasculitis are rifampin and pyrazinamide, while isoniazid is more commonly associated with drug-induced lupus [3]. However, it has been hypothesized that lupus and vasculitis induction may not be through two entirely different mechanisms in drug-induced syndromes [4]. In summary, we report a rare fatal case of systemic necrotizing vasculitis in a patient treated with isoniazid. Drugs should be included in the differential diagnosis of ANCA-associated vasculitides.
References [1] Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 Revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum 2013;65:1–11. [2] Csernok E, Lamprecht P, Gross W. Clinical and immunological features of druginduced and infection-induced proteinase 3-antineutrophil cytoplasmic antibodies and vasculitis. Curr Opin Rheumatol 2010;22:43–8. [3] Marzano AV, Vezzoli P, Crosti C. Drug-induced lupus: an update on its dermatologic aspects. Lupus 2009;18:935–40. [4] Wiik A. Drug-induced vasculitis. Curr Opin Rheumatol 2008;20:35–9.