Letters to the Editor / Joint Bone Spine 82 (2015) 66–73
Pulmonary hyalinizing granuloma associated with Sjögren syndrome and ANCA MPO vasculitis
a r t i c l e
i n f o
Keywords: Pulmonary hyalinizing granuloma Sjögren syndrome Myeloperoxidase-antineutrophil cytoplasmic antibodies ANCA MPO-associated vasculitis
We present the case of a 61-year-old woman with a history of asymptomatic bilateral pulmonary nodules detected in a routine chest X-ray (Fig. 1A). Anatomopathological study of one of the lung lesions obtained through thoracoscopic lung biopsy in 1989 led to a definitive diagnosis of pulmonary hyalinizing granuloma (PHG). Approximately 5 years after surgery, the patient reported a 1year history of xerophthalmia and xerostomia. Minor salivary gland biopsy showed Chisholm grade 3 sialadenitis; Ro/La-positive Sjögren syndrome was diagnosed. Ten years later the patient was admitted to our Rheumatology Department with fever, polyarthralgia, general fatigue, weight loss, calf muscle pain and paresthesia of the plantae. She did not report any respiratory or abdominal symptoms. On examination, the patient was febrile, pale, with minimal ankle edema. Cardiovascular, respiratory and abdominal examinations were all essentially normal. Admission laboratory studies showed hemoglobin of 8.4 g/dL, total white cell count of 9.90 × 10 × 9/L, platelet count of 509 × 10 × 9/L, elevated erythrocyte sedimentation rate of 115 mm/h, and C-reactive protein 196.64 mg/L. Positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPOANCA) were found. Urine examination showed numerous red blood cells and albuminuria. Blood creatinine was 11.0 mmol/L, which progressively increased to 15.8 mmol/L. Worsening renal failure and proteinuria prompted a renal biopsy that showed diffuse necrotizing glomerulonephritis without immune deposition in immune fluorescent study. Chest X-ray revealed that the pulmonary nodules had not increased in size or number. Conventional CT scan of the chest
71
also revealed multiple bilateral cystic lesions with thin walls, some containing coarse calcifications (Fig. 1B). Electromyography revealed mononeuropathy multiplex, and left gastrocnemius muscle biopsy showed necrotizing vasculitis. With a diagnosis of ANCA MPO-associated vasculitis, the patient was pulsed with intravenous methylprednisolone 1 g daily for 3 days followed by oral prednisolone and intravenous cyclophosphamide. Symptoms improved significantly. Serum creatinine level fell during the treatment and the patient was discharged in good clinical condition. At follow-up after 10 months, no clinical symptoms were observed. Pulmonary hyalinizing granuloma is an uncommon entity that consists of slowly enlarging nodular lesions in the pulmonary parenchyma. These lesions are typically asymptomatic. Chest radiography and CT findings show solitary or more often multiple, unilateral or bilateral nodules with well-defined borders. In this unusual case, CT scan showed cavitation and calcification that are rarely observed [1]. The etiology and pathogenesis remain unclear, but most authors have hypothesized that patients with PHG show evidence of underlying autoimmune phenomena [2–5]. Gorini et al. [6] reported the first case of pulmonary hyalinizing granulomas in which the patient had antineutrophil cytoplasmic autoantibodies with a granular cytoplasmatic pattern; they suggest that PHG could be regarded as a localized form of Wegener’s granulomatosis. Although the association with autoimmune diseases is known [2–4,6,7] we provide the first description of a patient with PHG associated with pANCA vasculitis and Sjögren syndrome. Our case supports the theory that PHG is associated with autoimmune phenomena and appears to corroborate the prolonged presence of immune complexes circulating in the pathogenesis of pulmonary lesions. Authorship contributions S. Rodriguez-Muguruza, S. Holgado and A. Olivé analyzed the data and wrote the paper. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
Fig. 1. Chest X-ray and CT scan of the chest showing multiple bilateral pulmonary nodules corresponding to pulmonary hyalinizing granuloma.
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Letters to the Editor / Joint Bone Spine 82 (2015) 66–73
References [1] Patel Y, Ishikawa S, MacDonnell KF. Pulmonary hyalinizing granuloma presenting as multiple cavitary calcified nodules. Chest 1991;100:170–221. [2] Yousem SA, Liselotte H. Pulmonary hyalinizing granuloma. Am J Clin Pathol 1987;87:1–6. [3] Engleman P, Liebow AA, Gmelich J, et al. Pulmonary hyalinizing granuloma. Am Rev Respir Dis 1977;115:997–1008. [4] Hashimoto S, Fuji W, Takahashi T, et al. Pulmonary hyalinizing granuloma with hydronephrosis. Intern Med 2002;41:463–6. [5] Chalaoui J, Gregoire P, Sylvestre J, et al. Pulmonary hyalinizing granuloma: a case of pulmonary nodules. Radiology 1984;152:23–6. [6] Gorinin M, Forloni F, Pezzoli A, et al. Pulmonary hyalinizing granuloma. A limited form of Wegener’s granulomatosis? Ann Ital Med Int 1998;13:176–9. [7] Shinohra T, Kaneko T, Miyazawa N, et al. Pulmonary hyalinizing granuloma with laryngeal and subcutaneous involvement: report of a case successfully treated with glucocorticoids. Int Med 2004;43:69–73.
Samantha Rodríguez-Muguruza ∗ Susana Holgado Alejandro Olivé Rheumatology Department, Carretera del Canyet s/n, Germans Trias i Pujol Hospital, 08916 Badalona, Spain ∗ Corresponding author. Tel.: +34 93 465 12 00×3288; fax: +34 93 497 88 43. E-mail addresses: sami [email protected], [email protected] (S. Rodríguez-Muguruza)
Accepted 6 June 2014 Available online 19 July 2014 http://dx.doi.org/10.1016/j.jbspin.2014.06.005
Is there a role for imatinib mesylate in the treatment of eosinophilic granulomatosis with polyangiitis?
a r t i c l e
i n f o
Keywords: Churg-Strauss syndrome Imatinib mesylate Anti-neutrophil cytoplasmic antibodies Eosinophilic granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic eosinophilic vasculitis, belonging to the group of ANCAassociated vasculitides (AAV). EGPA pathogenesis is still elusive, but a potential role for IL-5 and Eotaxins mediated eosinophil activation has been reported [1,2]. Imatinib mesylate, a tyrosine kinase (TK) inhibitor, is approved for the treatment of chronic myeloid leukaemia and FIP1L1/PDGFRA positive gene fusion hypereosinophilia. A potential role for imatinib in the treatment of idiopathic hypereosinophilic syndrome (HES) [3] and AAV has been recently proposed [4,5]. A 60-year-old white female with a 3-year history of non allergic asthma and sinusitis was admitted because of malaise, arthromyalgias, increasing breathlessness, cough and high spiking fever, rapidly followed by central and peripheral nervous system involvement. Laboratory examination showed marked peripheral eosinophilia (Fig. 1). Alveolitis with eosinophilia on bronchoalveolar lavage fluid was also demonstrated. Patient had negative workup for cancer, infections, and clonal eosinophilia. Immunofluorescence for ANCA resulted negative. A provisional diagnosis of HES was then made and a course of pulse high dose steroids followed by oral steroids were prescribed. After an initial clinical response, the recurrence of systemic and neurological symptoms along with eosinophilia at steroid tapering below 25 mg/day prompted off label prescription of imatinib. Normalization of eosinophilia alongside with complete clinical remission and steroid withdrawal were obtained just 1 month after imatinib introduction at the dose of 400 mg/day. During the following 12 months there were no safety concerns or drug-related adverse event and imatinib was gradually reduced to 100 mg/day. At the patients’ request imatinib was stopped after 13 months of therapy. Five months later, unexpectedly, the patient experienced disease relapse, including evanescent purpura, left foot mononeuritis and active urinary sediment. ANCA testing returned positive [pANCA 1:320, anti-MPO 80 UI/mL (normal value: < 15 UI/mL)]. A diagnosis of EGPA, fulfilling ACR criteria was then made and conventional immunosuppressive treatment was prescribed. In this case, persistence of complete clinical remission while on imatinib therapy and early relapse after imatinib withdrawal clearly suggests “on a clinical ground” that imatinib could provide a suitable therapeutic option for EGPA.
Fig. 1. Eosinophil blood count course and medications.
Pulmonary hyalinizing granuloma associated with Sjögren syndrome and ANCA MPO vasculitis
a r t i c l e
i n f o
Keywords: Pulmonary hyalinizing granuloma Sjögren syndrome Myeloperoxidase-antineutrophil cytoplasmic antibodies ANCA MPO-associated vasculitis
We present the case of a 61-year-old woman with a history of asymptomatic bilateral pulmonary nodules detected in a routine chest X-ray (Fig. 1A). Anatomopathological study of one of the lung lesions obtained through thoracoscopic lung biopsy in 1989 led to a definitive diagnosis of pulmonary hyalinizing granuloma (PHG). Approximately 5 years after surgery, the patient reported a 1year history of xerophthalmia and xerostomia. Minor salivary gland biopsy showed Chisholm grade 3 sialadenitis; Ro/La-positive Sjögren syndrome was diagnosed. Ten years later the patient was admitted to our Rheumatology Department with fever, polyarthralgia, general fatigue, weight loss, calf muscle pain and paresthesia of the plantae. She did not report any respiratory or abdominal symptoms. On examination, the patient was febrile, pale, with minimal ankle edema. Cardiovascular, respiratory and abdominal examinations were all essentially normal. Admission laboratory studies showed hemoglobin of 8.4 g/dL, total white cell count of 9.90 × 10 × 9/L, platelet count of 509 × 10 × 9/L, elevated erythrocyte sedimentation rate of 115 mm/h, and C-reactive protein 196.64 mg/L. Positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPOANCA) were found. Urine examination showed numerous red blood cells and albuminuria. Blood creatinine was 11.0 mmol/L, which progressively increased to 15.8 mmol/L. Worsening renal failure and proteinuria prompted a renal biopsy that showed diffuse necrotizing glomerulonephritis without immune deposition in immune fluorescent study. Chest X-ray revealed that the pulmonary nodules had not increased in size or number. Conventional CT scan of the chest
71
also revealed multiple bilateral cystic lesions with thin walls, some containing coarse calcifications (Fig. 1B). Electromyography revealed mononeuropathy multiplex, and left gastrocnemius muscle biopsy showed necrotizing vasculitis. With a diagnosis of ANCA MPO-associated vasculitis, the patient was pulsed with intravenous methylprednisolone 1 g daily for 3 days followed by oral prednisolone and intravenous cyclophosphamide. Symptoms improved significantly. Serum creatinine level fell during the treatment and the patient was discharged in good clinical condition. At follow-up after 10 months, no clinical symptoms were observed. Pulmonary hyalinizing granuloma is an uncommon entity that consists of slowly enlarging nodular lesions in the pulmonary parenchyma. These lesions are typically asymptomatic. Chest radiography and CT findings show solitary or more often multiple, unilateral or bilateral nodules with well-defined borders. In this unusual case, CT scan showed cavitation and calcification that are rarely observed [1]. The etiology and pathogenesis remain unclear, but most authors have hypothesized that patients with PHG show evidence of underlying autoimmune phenomena [2–5]. Gorini et al. [6] reported the first case of pulmonary hyalinizing granulomas in which the patient had antineutrophil cytoplasmic autoantibodies with a granular cytoplasmatic pattern; they suggest that PHG could be regarded as a localized form of Wegener’s granulomatosis. Although the association with autoimmune diseases is known [2–4,6,7] we provide the first description of a patient with PHG associated with pANCA vasculitis and Sjögren syndrome. Our case supports the theory that PHG is associated with autoimmune phenomena and appears to corroborate the prolonged presence of immune complexes circulating in the pathogenesis of pulmonary lesions. Authorship contributions S. Rodriguez-Muguruza, S. Holgado and A. Olivé analyzed the data and wrote the paper. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
Fig. 1. Chest X-ray and CT scan of the chest showing multiple bilateral pulmonary nodules corresponding to pulmonary hyalinizing granuloma.
72
Letters to the Editor / Joint Bone Spine 82 (2015) 66–73
References [1] Patel Y, Ishikawa S, MacDonnell KF. Pulmonary hyalinizing granuloma presenting as multiple cavitary calcified nodules. Chest 1991;100:170–221. [2] Yousem SA, Liselotte H. Pulmonary hyalinizing granuloma. Am J Clin Pathol 1987;87:1–6. [3] Engleman P, Liebow AA, Gmelich J, et al. Pulmonary hyalinizing granuloma. Am Rev Respir Dis 1977;115:997–1008. [4] Hashimoto S, Fuji W, Takahashi T, et al. Pulmonary hyalinizing granuloma with hydronephrosis. Intern Med 2002;41:463–6. [5] Chalaoui J, Gregoire P, Sylvestre J, et al. Pulmonary hyalinizing granuloma: a case of pulmonary nodules. Radiology 1984;152:23–6. [6] Gorinin M, Forloni F, Pezzoli A, et al. Pulmonary hyalinizing granuloma. A limited form of Wegener’s granulomatosis? Ann Ital Med Int 1998;13:176–9. [7] Shinohra T, Kaneko T, Miyazawa N, et al. Pulmonary hyalinizing granuloma with laryngeal and subcutaneous involvement: report of a case successfully treated with glucocorticoids. Int Med 2004;43:69–73.
Samantha Rodríguez-Muguruza ∗ Susana Holgado Alejandro Olivé Rheumatology Department, Carretera del Canyet s/n, Germans Trias i Pujol Hospital, 08916 Badalona, Spain ∗ Corresponding author. Tel.: +34 93 465 12 00×3288; fax: +34 93 497 88 43. E-mail addresses: sami [email protected], [email protected] (S. Rodríguez-Muguruza)
Accepted 6 June 2014 Available online 19 July 2014 http://dx.doi.org/10.1016/j.jbspin.2014.06.005
Is there a role for imatinib mesylate in the treatment of eosinophilic granulomatosis with polyangiitis?
a r t i c l e
i n f o
Keywords: Churg-Strauss syndrome Imatinib mesylate Anti-neutrophil cytoplasmic antibodies Eosinophilic granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic eosinophilic vasculitis, belonging to the group of ANCAassociated vasculitides (AAV). EGPA pathogenesis is still elusive, but a potential role for IL-5 and Eotaxins mediated eosinophil activation has been reported [1,2]. Imatinib mesylate, a tyrosine kinase (TK) inhibitor, is approved for the treatment of chronic myeloid leukaemia and FIP1L1/PDGFRA positive gene fusion hypereosinophilia. A potential role for imatinib in the treatment of idiopathic hypereosinophilic syndrome (HES) [3] and AAV has been recently proposed [4,5]. A 60-year-old white female with a 3-year history of non allergic asthma and sinusitis was admitted because of malaise, arthromyalgias, increasing breathlessness, cough and high spiking fever, rapidly followed by central and peripheral nervous system involvement. Laboratory examination showed marked peripheral eosinophilia (Fig. 1). Alveolitis with eosinophilia on bronchoalveolar lavage fluid was also demonstrated. Patient had negative workup for cancer, infections, and clonal eosinophilia. Immunofluorescence for ANCA resulted negative. A provisional diagnosis of HES was then made and a course of pulse high dose steroids followed by oral steroids were prescribed. After an initial clinical response, the recurrence of systemic and neurological symptoms along with eosinophilia at steroid tapering below 25 mg/day prompted off label prescription of imatinib. Normalization of eosinophilia alongside with complete clinical remission and steroid withdrawal were obtained just 1 month after imatinib introduction at the dose of 400 mg/day. During the following 12 months there were no safety concerns or drug-related adverse event and imatinib was gradually reduced to 100 mg/day. At the patients’ request imatinib was stopped after 13 months of therapy. Five months later, unexpectedly, the patient experienced disease relapse, including evanescent purpura, left foot mononeuritis and active urinary sediment. ANCA testing returned positive [pANCA 1:320, anti-MPO 80 UI/mL (normal value: < 15 UI/mL)]. A diagnosis of EGPA, fulfilling ACR criteria was then made and conventional immunosuppressive treatment was prescribed. In this case, persistence of complete clinical remission while on imatinib therapy and early relapse after imatinib withdrawal clearly suggests “on a clinical ground” that imatinib could provide a suitable therapeutic option for EGPA.
Fig. 1. Eosinophil blood count course and medications.
