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An Uncommon Cause of Hiccup: Sarcoidosis

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An Uncommon Cause of Hiccup: Sarcoidosis Acta Medica Mediterranea, 2013, 29: 707 AN UNCOMMON CAUSE OF HICCUP: SARCOIDOSIS EBRU UNLU1, SEVINC SARINC ULASLI2, EMRE KACAR1, NAZAN OKUR1, ERSIN GUNAY2 1Department of Radiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey - 2Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. ABSTRACT A 28 year-old male presented with hiccup of 2 months duration. His physical examination was unremarkable. Laboratory investigations revealed elevated angiotensin converting enzyme (ACE) levels. Chest radiography revealed bilateral infiltrations and hilar enlargements. Thorax computed tomography (CT) revealed enlarged mediastina lymph nodes and bilateral reticulonodular densities distributed more densely in the upper lung fields. Bronchoscopy was performed and non-caseating granuloma was deter- mined in pathologic examination. Bronchoalveolar lavage cultures for tuberculosis and fungal infections were negative. We diag- nosed patient as sarcoidosis due to mediastinal lymph node enlargement, non-caseating granuloma, exclusion of tuberculosis and fungal infections and elevated serum ACE level. Magnetic resonance imaging of brain revealed well-circumscribed lesion on the dorsal side of medulla. We conclude that the long-standing hiccup may be due to enlarged mediastina lymph node and/or neurosar- coidosis. Therefore physicians should keep in mind the diagnosis of sarcoidosis in patients presenting with hiccup. Key words: Bronchoalveolar lavage, sarcoidosis, hiccup. Received August 27, 2013; Accepted Septemper 20, 2013 Introduction temic diseases. He was doing woodwork for 10 years. Hiccup reflex arc has an afferent pathway, He did not have headaches, cough, abdominal including the vagus, phrenic nerves, sympathetic pain, fever or body weight loss. He had no periph- chain and has an efferent pathway, including the eral lymphadenopathies, hepatomegaly, phrenic nerve(1). Lesions in this pathway may cause splenomegaly and skin lesions. His respiratory hiccups. Hiccups can be seen because of central and sounds were normal. Neurological examination peripheral lesions, and also diaphragmatic irritation. revealed no pathology. Complete blood count, liver However, the central neuroanatomical localization functions, renal functions, serum calcium and of hiccups is not exactly known(2). Hiccup is rarely tumor markers were within normal limits. seen in sarcoidosis(3). Here we present a case of sar- Angiotensin converting enzyme (ACE) level of coidosis with an extremely rare symptom-hiccup. serum was increased up to 33 IU/L (normal value; 8.3-21.4 IU/L ). Chest radiography revealed bilater- Case report al infiltrations and hilar enlargements (figure 1). Thorax CT showed multiple enlarged mediastina A 28 year-old male was admitted to the gas- lymph nodes and bilateral reticulonodular densities troenterology outpatient clinic of our university distributed more densely in the upper lung fields hospital because of hiccups of 2 months duration. (figures 2,3). Pulmonary function tests revealed the He was consulted to the department of pulmonary presence of a restrictive ventilator defect. diseases due to the symptom of shortness of breath. Bronchoscopy was performed. No endobronchial He had 3-pack year smoking history and no sys- lesion was observed. Bronchoalveolar lavage 708 Ebru Unlu, Sevinc Sarinc Ulasli et Al (BAL) and parenchymal biopsy were obtained from right middle lobe. Pathological examination of parenchymal biopsy revealed non-caseating granu- lomas, BAL for tuberculosis and fungal infections were negative. CD4/CD8 ratio in BAL was 5. Figure 4a-4b: MRI of brain revealed well-circumscribed lesion on the dorsal side of medulla, which was hyperin- tense on T2-weighted sequences that enhanced on post- gadolinium T1-weighted MRI. Figure 1: Chest radiography revealed diffuse multiple Discussion micronodules in both lungs. Sarcoidosis is a granulomatous systemic dis- ease with the symptoms of low-grade fever, cough, dyspnea and arthralgia(4-6). Systemic signs of sar- coidosis are bilateral enlarged hilar lymphadenopa- thy, diffuse pulmonary infiltration, skin lesions, liver and eye involvement(4,7). Diagnosis of sar- coidosis includes clinical and radiographic features, together with non-caseating granulomas in patho- logic examination(4,5,8). We diagnosed our patient as Figure 2a-2b: Axial CT scan shows multiple mediastina sarcoidosis due to mediastina lymph node enlarge- lymphadenopathy. ment, non-caseating granuloma, exclusion of tuber- culosis and fungal infections and elevated serum ACE level. In addition, neurologic involvement is seen in approximately 5% of patients with sarcoidosis and half of these patients can be referred with the neu- rologic symptoms(4,9). The most common features of neurosarcoidosis are peripheral neuropathies of cra- nial nerves and diabetes insipidus(9,10). Figure 3: Axial CT scan shows bilateral multiple micro- Neurosarcoidosis primarily involves the lep- nodules. tomeninges but parenchymal invasion often occurs(7). MRI of brain revealed well-circumscribed Magnetic resonance imaging (MRI) of brain lesion on the dorsal side of medulla, which was revealed well-circumscribed lesion on the dorsal hyperintense on T2-weighted sequences. The lesion side of medulla, which was hyperintense on T2- was enhanced on post-gadolinium on T1-weighted weighted sequences and on post-gadolinium T1- images and there was no restricted diffusion. weighted images the lesion was enhanced. (figures In the literature, the cause of hiccups in two 4,5). Moreover there was no restricted diffusion. reported sarcoidosis patients was attributed to cen- Mediastina lymph node enlargement, non- tral nervous system involvement and moreover hic- caseating granuloma in parenchymal biopsy, exclu- cup was not the initial symptom(10,11). One of the sion of tuberculosis and fungal infections, and an largest series of patients with neurosarcoidosis elevated serum ACE level were the diagnostic fea- reported no cases of hiccups as an initial symp- tures of sarcoidosis. The patient received systemic tom(12). On the other hand there has been only one steroid treatment. His hiccups were resolved at the report of sarcoidosis with the presentation of only first week of steroid treatment. hiccups and it is thought to be due to mediastina An uncommon cause of Hiccup: Sarcoidosis 709 lymphnodes(13). Souadjian and Cain have evaluated 2) John S, Parambil J, Culver D, Tavee J. Medullary 220 cases of hiccup and found only one case of sar- neurosarcoidosis presenting with intractable hic- coidosis(3). Only two other reports described hiccups coughs. J Clin Neurosci 2012; 19: 1193-5. in systemic sarcoidosis and were thought to be due 3) Souadjian JV, Cain JC. Intractable hiccup, etio- logical factors in 220 cases. Postgrad Med 1968; to mediastina lymphadenopathy(13) and peritoneal 43: 72-7. nodules(14). 4) Baughman RP, Teirstein AS, Judson MA, A case report by Kondo et al. described a sar- Rossman MD, Yeager H Jr, Bresnitz EA, et al. coidosis patient with intractable hiccups and Clinical characteristics of patients in a case-con- resolved with steroid treatment(10). They believed trol study of sarcoidosis. Am J Respir Crit Care that central nervous system involvement was Med 2001; 164: 1885-9. responsible for hiccups however they were not able 5) Gupta SK, Gupta S. Sarcoidosis in India: a review to confirm this hypothesis by CT scan or MRI. of 125 biopsy-proven cases from eastern India. Another sarcoidosis case with hiccup was Sarcoidosis 1990 ;7: 43-9. reported by Connolly et al. Their patient had lep- 6) Adedayo AO, Grell GA, Bellot P. Severe refracto- tomeningeal enhancement around multiple cranial ry sarcoidosis in a 64-year-old man with persis- tent leucopenia. West Indian Med J 2003; 52: 56- nerves both in the midbrain and high cervical spinal 8. (11) cord . Our patient with biopsy-proven sarcoidosis 7) Dennis AN, Darius CW. Neurosarcoidosis: a presented only with hiccups and he had both medi- review of its intracranial manifestation. J Neurol astina lymphnodes which may compress phrenic 2001; 248: 363-72. nerve and lesion in dorsomeduller medulla; the 8) Ozbudak O, Ozbudak IH, Wang KP. Association region of multiple cranial nerves together with sur- Between Acute Myeloblastic Leukaemia and rounding the presumed “hiccup centre” in the mid- Sarcoidosis. West Indian Med J 2009; 58: 185-7. brain or high cervical spinal cord. To the best of our 9) Oksanen V. Neurosarcoidosis: Clinical presenta- knowledge; there have been no reports of sarcoido- tions and course in 50 patients. Acta Neurol sis presenting with hiccups and have both mediasti- Scand 1986; 73: 283-90. 10) Kondo T, Tanigaki T, Suzuki H, Tamaya S, Ohta na lymphnodes and neurosarcoidosis till our case Y, Yamabayashi H. Long-standing hiccup in a report. patient with sarcoidosis. Jpn J Med 1989; 28: Steroids are the corner stone treatment for 212-215. CNS involvement like systemic sarcoidosis(15). 11) Connolly JP, Craig TJ, Sanchez RM, Sageman Immunosuppressive agents and radiotherapy are WS, Osborn RE. Intractable hiccups as a presen- alternative treatment regimens(15). Treatment with tation of central nervous system sarcoidosis. West immunosuppressive agents and steroids can be J Med 1991; 155: 78-9. more beneficial for resolving symptoms than treat- 12) Delaney P. Neurologic manifestations in sar- ment with steroids alone. Different responses of coidosis: Review of the literature with a report of neurosarcoidosis to steroid therapy have
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