Sarcoidosis of Tongue: A Rare of the Rarest Case Report  

Abhishek Singh Nayyar
Department of Internal Medicine, University hospital of La Rabta, Tunis, Tunisia
Author    Correspondence author
International Journal of Clinical Case Reports, 2015, Vol. 5, No. 26   doi: 10.5376/ijccr.2015.05.0026
Received: 10 May, 2015    Accepted: 15 Jun., 2015    Published: 02 Jul., 2015
© 2015 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abhishek Singh Nayyar, 2015, Sarcoidosis of Tongue: A Rare of the Rarest Case Report, International Journal of Clinical Case Reports, 5(26) 1-4 (doi: 10.5376/ijccr.2015.05.0026)

Abstract

Sarcoidosis is a multisystem inflammatory disease of unknown etiology that predominantly affects the lungs and intra-thoracic lymph nodes. Sarcoidosis is manifested by the presence of non-caseating granulomas in affected organs and tissues. A 40 year old male patient with lesions in tongue and the palate was examined. Clinical signs were recorded and incisional biopsies from the tongue were taken. The diagnosis of sarcoidosis was established by the histopathological evidence of typical non-caseating granulomas from tissue biopsy, supported by an elevated serum Angiotensin Converting Enzyme (S-ACE) value of 62.4 U/L and 24hr. urine calcium of 538 mg.

Keywords
Sarcoidosis; Chronic granulomatous; Langerhans cells

Although sarcoidosis has been identified as a specific disease entity for more than a century, the specific cause of sarcoidosis is still unknown. In addition, the diagnostic criteria, treatment algorithms, method of follow-up and natural course of the disease have not been clearly elucidated (Sharma, 2008).

Sarcoid granulomas are thought to result from the interaction of an antigen with the immune system (Hunninghake et al., 1999). It has been conjectured that granulomatous inflammation in sarcoidosis is necessary to clear the antigen (Chen et al., 2010). If this theory is supposed to be correct, it is plausible that an effective anti-sarcoidosis therapy may resolve granulomatous inflammation that may result in failure of clearance of the putative sarcoidosis antigen(s). In this scenario, when treatment is withdrawn, the antigen may still be present and could lead to recurrent granulomatous inflammation and, therefore, relapse (Panselinas and Judson, 2012).This schema is supported by data that suggest that a relapse of sarcoidosis is more common in patients previously treated for sarcoidosis (Gottlieb et al., 1997),or with higher doses of corticosteroids (Rizzato et al., 1998). In addition, this concept is consistent with the premise that anti-sarcoidosis treatment improves granulomatous inflammation but does not alter the natural course of the disease process (Israel et al., 1973; Eule et al., 1986; Zaki et al., 1987; Lower and Baughman, 1995; Paramothayan et al., 2005; Panselinas et al., 2009; Chen et al., 2010). Therefore, the granulomatous inflammation of sarcoidosis may be beneficial and should probably be left unsuppressed, provided that it does not result in significant patient symptoms or organ dysfunction. When treatment is indicated for sarcoidosis, corticosteroids are considered the drug of choice because they appear to have the greatest likelihood of efficacy and work most rapidly (Schutt et al., 2010). Although corticosteroids are currently entrenched as the drug of choice for most forms of sarcoidosis, alternative agents are often used because of the frequency of the development of corticosteroid side effects. The diagnosis of sarcoidosis remains a challenging issue principally because there is no specific and reliable diagnostic test available to date. Various algorithms and criteria have been established as diagnostic guidelines that may be useful while the development of a gold standard diagnostic test yet needs to be worked-out. Oral involvement in sarcoidosis is very rare. The first oral lesion of sarcoidosis was reported in 1942 by Schroff. To our knowledge there are only 7 cases of Sarcoidosis of tongue reported to date (Koike, 2007).
Case Report
A 40 year old male patient reported to the Department of Oral Medicine and Radiology with the chief complaint of missing teeth. The past medical history of the patient revealed that the patient had some severe breathing problem few years ago for which he was kept on a long treatment protocol and a follow-up for quite some years. He was also subjected to repeated chest radiography during the same time.
Intra-oral examination of the patient revealed a multi-lobulated growth in relation to the dorsal aspect of the tongue which presented with irregular margins and mimicked the clinical picture of that of median rhomboid glossitis (Figure 1) in addition to a few erythematous areas in relation to the corresponding parts of the palate. Incisional biopsies were taken from the tongue from two different areas which revealed non-caseating epithelioid granulomas infiltrated with “Langerhans cell type of multinucleated giant cells”. Since the histopathological findings were compatible with sarcoidosis, in order to confirm the diagnosis, serum Angiotensin Converting Enzyme (S-ACE) and 24 hr. urine calcium were advised which revealed an elevated serum Angiotensin Converting Enzyme (S-ACE) value of 62.4 U/L (normal value: 18-55 U/L) and a 24 hr. urine calcium of 538 mg (normal value <180 mg). Chest radiography revealed bilateral linear fibrotic strands with hilar vascular shadows (Figure 2) Acid-fast bacilli were not found in smears from specimens of the tongue and culture for isolation of Mycobacteria sp. in Löwenstein-Jensen medium was negative. The radiograph of the maxillofacial region did not reveal any abnormality. Based on the above laboratory findings, the diagnosis of sarcoidosis was established. The patient was then referred to the higher centre for further investigation, opinion and needful.


Figure 1



Figure 2


D
iscussion
Sarcoidosis is a multisystem inflammatory disease process of unknown etiology that predominantly affects the lungs and intra-thoracic lymph nodes. Sarcoidosis is manifested by the presence of non-caseating granulomas in affected organs and tissues. It is characterized by a seemingly exaggerated immune response against a difficult-to-discern antigen (Ten Berge et al., 2012). T cells play a central role in the development of sarcoidosis as they likely propagate an excessive cellular immune reaction. There has been seen an active accumulation of CD4 cells at the sites of disease activity accompanied by the release of interleukin (IL)-2. This may manifest clinically by an inverted CD4/CD8 ratio (Mota et al., 2012). Moreover, both, tumor necrosis factor (TNF) and TNF receptors, are increased in this disease. In addition to T cells, there is evidence of B cell hyperreactivity too with intense immunoglobulin production, the levels of which tend to be significantly higher in the active than in inactive stages of the disease and correlate with serum angiotensin-converting enzyme (ACE) levels which are significantly elevated during the active phases of the disease process (Ogisu, 2001). Active sarcoidosis has also been associated with plasmatic hypergammaglobulinemia (Hunninghake and Crystal, 1981).
The exact cause of the disease though is still not known; however, both genetic and environmental factors seem to play important roles (Sverrild et al., 2008) as also, it is well-known that sarcoidosis is neither a malignant nor an autoimmune disease process.
The clinical presentation in sarcoidosis varies with the extent and severity of the disease from being asymptomatic in approximately 5% of the cases to vague, systemic complaints in the form of fever and anorexia in around 45% of cases, pulmonary complaints of dyspnea, cough, chest pain and hemoptysis, though rare, in approximately 50% of cases, Löfgren syndrome with clinical manifestations in the form of fever, bilateral hilar lymphadenopathy and polyarthralgias and variable dermatological and ocular manifestations depending on the extent of involvement of the affected viscera and disease severity. Ocular involvement, although extremely rare, may lead to blindness, if left untreated. Other possible manifestations might also include gross osseous involvement, heart failure due to cardiomyopathy, heart block and sudden death, lymphocytic meningitis and cranial nerve palsies and hypothalamic/pituitary dysfunction, again though seen rarely, mandating immediate attention and being a cause of dreaded prognosis with high mortality and morbidity. Clinically, sarcoidosis may present in an acute, sub-acute or chronic fashion. Distinct presentations of sarcoidosis are associated with different clinical courses with approximately 50% of the patients undergoing remission usually within a span of 2-3 years without any active intervention or, treatment. The other 50% of the patients have persistent, generally progressive disease requiring treatment to mitigate the consequences of unremitting inflammation and subsequent fibrosis in the specific visceral organs affected, most commonly, the lungs.
The diagnosis requires histologic evidence of granulomatous inflammation, exclusion of alternative causes, and evidence of systemic disease. Because there is no available diagnostic test for sarcoidosis, the diagnosis is never completely secure. Routine laboratory investigations are often unrevealing but possible abnormalities includehypercalcemia in about 10-13% of patients and hypercalciuria in about a third of patients (Inui et al., 2001; Kavathia et al., 2010) to elevated serum angiotensin-converting enzyme (ACE) (Miyoshi et al., 2010) and alkaline phosphatase (Cremers et al., 2012) levelsthat are consistently raised during the active phases of the disease process. Hypercalcemia or hypercalciuria may occur due to non-caseating granulomas that secrete active form of vitamin D. An elevated alkaline phosphatase level could suggest hepatic involvement. Elevated serum ACE levels may be explained on the basis of the hypothesis that non-caseating granulomas secrete ACE which may function as a cytokine. Infact, serum ACE levels may correlate with total body granuloma load. Serum ACE levels are elevated in 60% of patients at the time of diagnosis. Levels may be increased in fluid from bronchoalveolar lavage or in cerebrospinal fluid however, there is no clear prognostic value.
A chest radiograph is central to evaluation. The ultimate diagnosis however requires histologic evidence of granulomatous inflammation with possible exclusion of alternative etiologies and added evidence of systemic disease. The central histologic finding is the presence of non-caseating granulomas with special stains negative for fungui and mycobacteria.
Most patients require only symptomatic therapy with NSAIDs although approximately 10% of the patients need treatment for extra-pulmonary disease and 15% of patients require treatment for persistent pulmonary disease. Corticosteroids are the mainstay of therapy while some data suggest that corticosteroid use may be associated with increased relapse rates in addition to the well-known adverse effect profiles. Although corticosteroids are used for symptom relief and remain the mainstay of treatment, their efficacy in this disease is still unclear. For patients with advanced pulmonary fibrosis from sarcoidosis, lung transplantation remains the only course for long-term survival (Arcasoy et al., 2001). Alternative therapies include methotrexate (MTX), anti-malarials, chloroquine and hydroxychloroquine, cyclophosphamide which has been used as a steroid-sparing treatment in patients with refractory sarcoidosis, azathioprine, chlorambucil which may be beneficial in patients with progressive disease unresponsive to corticosteroids and in case, they are contraindicated, cyclosporine which may be of benefit in progressive sarcoidosis resistant to conventional therapy in addition to infliximab and thalidomide which have been used for refractory sarcoidosis, particularly for cutaneous disease, as well as for the long-term management of extra-pulmonary sarcoidosis.
The oral lesions may be solitary or, multiple and are seen as a part of the generalized disease process (Suresh and Radfar, 2005). In some cases, oral involvement is the first, or only, manifestation of the disease (Al-Azri et al., 2012). Most of the lesions are seen to spontaneously resolve with time with the start of systemic therapy while some authors also suggest surgical excision for treatment of the oral soft tissue or jaws lesions (Piattelli et al., 1998; Batal et al., 1999).
Conclusion
Although very rare, oral lesions of sarcoidosis may be the first or, the only presenting manifestations of this complex disease process. This multisystem disorder can never be completely cured, so, a periodic follow-up of the patients becomes almost mandatory in the evaluation of the disease during the course taken by it for its effective management and to avoid any subsequent complications, ruling-out their possibility at the earliest.
References
Al-Azri A.R., Logan R.M., and Goss A.N.,, 2012, Oral Lesion as the first clinical presentation in Sarcoidosis: A Case Report, Oman Med. J., 27: 243-245
http://dx.doi.org/10.5001/omj.2012.55
Arcasoy S.M., Christie J.D., Pochettino A., Rosengard B.R., Blumenthal N.P., Bavaria J.E., et al., 2001, Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation, Chest,120:873-880
http://dx.doi.org/10.1378/chest.120.3.873
Batal H., Chou L.L., and Cottrel D.A., 1999, Sarcoidosis: Medical and dental implications, Oral Surg Oral Med Oral Pathol Oral Radiol Endod., 88:386-390
http://dx.doi.org/10.1016/S1079-2104(99)70049-1
Chen E.S., Song Z., Willett M.H., Heine S., Yung R.C., Liu M.C., Groshong S.D., Zhang Y., Tuder R.M., and Moller D.R., 2010, Serum amyloid A regulates granulomatous inflammation in sarcoidosis through Toll-like receptor-2, Am. J. Respir Crit Care Med.181:360-373
http://dx.doi.org/10.1164/rccm.200905-0696OC
Cremers J., Drent M., Driessen A., Nieman F., Wijnen P., Baughman R., et al., 2012, Liver-test abnormalities in sarcoidosis, Eur. J. Gastroenterol. Hepatol., 24:17-24
http://dx.doi.org/10.1097/MEG.0b013e32834c7b71
Eule H., Weinecke A., Roth I., and Wuthe H., 1986, The possible influence of corticosteroid therapy on the natural course of pulmonary sarcoidosis: Late results of a continuing clinical study, Ann. N Y Acad. Sci., 465:695-701
http://dx.doi.org/10.1111/j.1749-6632.1986.tb18548.x
Gottlieb J.E., Israel H.L., Steiner R.M., Triolo J., and Patrick H., 1997, Outcome in sarcoidosis: The relationship of relapse to corticosteroid therapy, Chest, 111:23-631
http://dx.doi.org/10.1378/chest.111.3.623
Hunninghake G.W., and Crystal R.G., 1981, Mechanisms of hypergammaglobulinemia in pulmonary sarcoidosis, Site of increased antibody production and role of T lymphocytes, J. Clin. Invest., 67:86-92
http://dx.doi.org/10.1172/JCI110036
Hunninghake G.W., Costabel U., Ando M., Baughman R., Cordier J.F., Du B.R., Eklund A., Kitaichi M., Lynch J., Rizzato G., Rose C., Selroos O., Semenzato G., and Sharma O.P., 1999, ATS/ERS/WASOG statement on sarcoidosis, American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders, Sarcoidosis Vasc Diffuse Lung Dis.,16:149-173
Inui N., Murayama A., Sasaki S., Suda T., Chida K., Kato S., et al., 2001, Correlation between 25-hydroxyvitamin D3 1 alpha-hydroxylase gene expression in alveolar macrophages and the activity of sarcoidosis, Am, J, Med,, 110:687-693
http://dx.doi.org/10.1016/S0002-9343(01)00724-0
Kavathia D., Buckley J.D., Rao D., Rybicki B., and Burke R., 2010, Elevated 1, 25-dihydroxyvitamin D levels are associated with protracted treatment in sarcoidosis, Respir. Med., 104:564-570
http://dx.doi.org/10.1016/j.rmed.2009.12.004
Israel H.L., Fouts D.W., and Beggs R.A., 1973, A controlled trial of prednisone treatment of sarcoidosis, Am. Rev. Respir. Dis.,107:609-614
Koike K., 2007, Sarcoidosis of tongue: A case report, Auris. Nasus. Larynx, 34:131-133
http://dx.doi.org/10.1016/j.anl.2006.09.008
Lower E.E., and Baughman R.P., 1995, Prolonged use of methotrexate for sarcoidosis, Arch. Intern. Med., 155:846-851
http://dx.doi.org/10.1001/archinte.155.8.846
http://dx.doi.org/10.1001/archinte.1995.00430080088011
Miyoshi S., Hamada H., Kadowaki T., Hamaguchi N., Ito R., Irifune K., et al., 2010, Comparative evaluation of serum markers in pulmonary sarcoidosis, Chest, 137:1391-1397
http://dx.doi.org/10.1378/chest.09-1975
Mota P.C., Morais A., Palmares C., Beltrão M., Melo N., Santos A.C., et al., 2012, Diagnostic value of CD103 expression in bronchoalveolar lymphocytes in sarcoidosis, Respir. Med., 106:1014-1020
http://dx.doi.org/10.1016/j.rmed.2012.03.020
Ogisu N., Sato S., Kawaguchi H., Sugiura Y., Mori T., Niimi T., et al., 2001, Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis, Intern. Med. 40:201-207
http://dx.doi.org/10.2169/internalmedicine.40.201
Panselinas E., and Judson M.A., 2012, Acute pulmonary exacerbations of sarcoidosis, Chest,142:827-836
http://dx.doi.org/10.1378/chest.12-1060
Panselinas E., Rodgers J.K., and Judson M.A., 2009, Clinical outcomes in sarcoidosis after cessation of infliximab treatment, Respirology, 14:522-528
http://dx.doi.org/10.1111/j.1440-1843.2009.01518.x
Paramothayan N.S., Lasserson T.J., and Jones P.W., 2005, Corticosteroids for pulmonary sarcoidosis, Cochrane Database Syst. Rev., CD001114
http://dx.doi.org/10.1002/14651858.cd001114.pub2
Piattelli A., Favia G.F., and DiAlberti L., 1998, Oral ulceration as a presenting sign of unknown sarcoidosis mimicking a tumour: Report of 2 cases, Oral Oncol., 34:427-430
http://dx.doi.org/10.1016/S1368-8375(98)00041-4
Rizzato G., Montemurro L., and Colombo P., 1998, The late follow-up of chronic sarcoid patients previously treated with corticosteroids, Sarcoidosis Vasc Diffuse Lung Dis., 15:52-58
Schutt A.C., Bullington W.M., and Judson M.A., 2010, Pharmacotherapy for pulmonary sarcoidosis: A Delphi consensus study, Respir. Med., 104:717-723
http://dx.doi.org/10.1016/j.rmed.2009.12.009
Sharma O.P., 2008, Sarcoidosis around the world, Clin. Chest Med., 29:357-363
http://dx.doi.org/10.1016/j.ccm.2008.03.013
Suresh L., and Radfar L., 2005, Oral Sarcoidosis: A review of literature, Oral Diseases, 11:138-145
http://dx.doi.org/10.1111/j.1601-0825.2005.01014.x
Sverrild A., Backer V., Kyvik K.O., Kaprio J., Milman N., and Svendsen C.B., 2008, Heredity in sarcoidosis: A registry-based twin study, Thorax, 63:894-896
http://dx.doi.org/10.1136/thx.2007.094060
Ten Berge B., Kleinjan A., Muskens F., Hammad H., Hoogsteden H.C., Hendriks R.W., et al., 2012, Evidence for local dendritic cell activation in pulmonary sarcoidosis, Respir. Res., 13:33
http://dx.doi.org/10.1186/1465-9921-13-33

Zaki M.H., Lyons H.A., Leilop L., and Huang C.T., 1987, Corticosteroid therapy in sarcoidosis: A five-year controlled follow-up study, N Y State J. Med., 87:496-499

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