|Ahead of print publication
Single-organ sarcoidosis involving hepatic, lacrimal, and cardia
BN Shiva Prasad1, Ravi Puranik2, Venugopal Anandaswamy3, P Jayakumar4
1 Consultant Rheumatologist, Apollo BGS Hospital, Mysore, Karnataka, India
2 Consultant Physician, Apollo BGS Hospital, Mysore, Karnataka, India
3 Consultant Pathologist, Apollo BGS Hospital, Mysore, Karnataka, India
4 Consultant Cardiologist, Apollo BGS Hospital, Mysore, Karnataka, India
BN Shiva Prasad,
Apollo BGS Hospital, Mysore, Karnataka
Source of Support: None, Conflict of Interest: None
Sarcoidosis is a multisystem idiopathic granulomatous disease. Lung is the most common organ involved but can involve any organ. The skin, eyes, joints, and heart are affected in a significant fraction of patients. Extrapulmonary sarcoidosis may be the major manifestation of the disease. Extrapulmonary disease may manifest before, concurrent with, or after the development of pulmonary disease or as isolated independent disease. We present three cases of isolated organ sarcoidosis involving the liver, lacrimal, and heart. Isolated organ involvement is difficult to diagnose and the treatment of Isolated organ is not defined.
Keywords: Extra-pulmonary, non Caseating granulomatous disease, Sarcoidosis
| Introduction|| |
Sarcoidosis is a multisystem idiopathic granulomatous disease. Lung is the most common organ involved but can involve any organ. The skin, eyes, joints, and heart are affected in a significant fraction of patients. Extrapulmonary sarcoidosis may be the major manifestation of the disease. Extrapulmonary disease may manifest before, concurrent with, or after the development of pulmonary disease. The manifestations vary from asymptomatic lesions involving skin to life-threatening condition if cardiac is involved. Isolated Extra-pulmonary sarcoidosis was observed in only 2% of cases., The prevalence of extrapulmonary sarcoidosis varies among populations and also the organ system involvement. The manifestation varies with age, race, familial, and sex., We present three cases of extrapulmonary isolated organ involvement of sarcoidosis.
| Case Reports|| |
A 65-year-old lady, hypertensive for 25 years and diabetic for 15 years, presented with abdominal discomfort and nausea for nine months duration. She had loss of appetite and loss of weight of 12 kg in 9 months. She had generalized weakness and easy fatiguability. There was no history of fever, skin lesion, pedal edema, red-eye, oral ulcers, epistaxis, chest pain, breathlessness, or facial swelling. General and systemic examination was normal. On evaluation, she was found to have increased serum alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) [Table 1], but no reason was found. It was thought to be metformin induced and was initiated on insulin. Two months later, she had increased nausea, and during evaluation, she was found to have elevated creatinine and hypercalcemia [Table 1]. She had hepatomegaly, 5 cm below right costal margin, firm, and tender. At this juncture, she was thought to have isolated hepatic disease such as autoimmune hepatitis (Hep), granulomatous liver disease, or having paraneoplastic disease. She was evaluated for the causes of hypercalcemia and to rule out malignancy. Parathyroid hormone was normal. She was treated with zolendronate for hypercalcemia with fluid support. Renal functions improved. Her ALP and GGT were still elevated. Other biochemical parameters were normal. Positron-emission tomography–computed tomography (PET CT) done to look for any malignancy revealed diffusely increased fluorodeoxyglucose intake seen in the liver, no avid mass or lymph nodes [Figure 1], and no occult neoplasm. Liver biopsy was done. Histopathology revealed that granulomatous inflammation [Figure 2], acid-fast bacilli (AFB) stain, and tuberculosis polymerase chain reaction (TB PCR) were negative. The Mantoux test was negative. Human immunodeficiency virus and Hep B and C serology were negative. Serum angiotensin-converting enzyme (ACE) levels were elevated [Table 1].
|Figure 1: PET CT of whole body revealing grossly enlarged Liver with no other mass lesion|
Click here to view
|Figure 2: Liver biopsy revealing non caseating granuloma with asteroid bodies|
Click here to view
A diagnosis of isolated hepatic sarcoidosis was made, and the patient was treated with oral prednisolone 30 mg with tapering doses and azathioprine 100 mg/day with ursodeoxycholic acid. This case was followed up for 2 years, and there was no relapse of disease.
A 52-year-old male hypertensive complained of swelling in the right upper eyelid for 2 months gradually increased in size causing drooping of the eyelid [Figure 3]. There was no pain, redness or decreased visual acuity but felt fullness in the eye. There were no fever, skin rash, breathlessness, chest pain, loss of weight/appetite, abdominal pain, and joint pains. There was no history of facial or ocular trauma, sinus or skin infections, or ocular surgeries. General and systemic examination was normal. Partial ptosis of the right eyelid was present but no neurological/visual defects. Extraocular movements were normal. A soft mass could be palpated over the right eyelid. On evaluation, complete hemogram, biochemical, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) evaluation was normal. CT of the right eye revealed ill-defined thickening of the lacrimal gland on the right side with contrast enhancement and subcutaneous infiltration with possible pseudotumor of the lacrimal gland [Figure 3]. Serology for antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibody was negative. Biopsy of the mass revealed granulomatous inflammation with occasional Langhans giant cells without caseation. No necrosis or foreign body was identified and negative for malignancy. AFB stain and TB PCR of the tissue were negative. Serum ACE levels were 55.8 IU/l (8–52). Chest X-ray and CT of the chest and abdomen were normal. A diagnosis of isolated lacrimal gland sarcoidosis was made, and the patient was treated with oral prednisolone 30 with tapering doses and azathioprine at 100 mg/day. The case was followed for 2 years. There was complete recovery of the swelling and no relapse of the disease.
|Figure 3: Upper panel-showing partial Ptosis of the right eye. Lower panel-CT scan of the orbits revealing lacrimal enlargement of the right side |
Click here to view
A 28-year male presented with on and off palpitations for 6 months. This was associated with giddiness and fatigability during the episode. There were no syncope/dyspnea and no other general or systemic symptoms. General and systemic examination was normal. His pulse was 68/min and blood pressure was 130/70 mmHg. Electrocardiography and echocardiography were normal. Holter revealed monophasic ventricular polymorphic complexes. Cardiac magnetic resonance imaging (MRI) was done. Early gadolinium enhancement study in the short axis revealed small foci of delayed enhancing areas in the posterolateral aspect of the basal cavity region adjacent to the left ventricular outlet tract in the epicardium, suggestive of sarcoidosis [Figure 4]. Similar MRI picture can be present in Amyloidosis also. His hemogram, biochemical test, and thyroid profile was normal. ESR was 80 mm/1st h and CRP was 12 mg/L (6 mg/L). Serum ACE level was 27 IU/L (8–52 IU/L). Serum and urine electrophoresis did not reveal “M” spike, and abdominal fat pad was negative for amyloidosis, so ruled out amyloidosis. CT of the chest and abdomen was normal. The Mantoux test was negative. A diagnosis of isolated cardiac sarcoid was made. He was treated with anti-arrythmic drugs – metaprolol and amiodarone, with prednisolone 25 with mg/day tapering doses and azathioprine of 100 mg/day. The patient was followed for 2 years. Repeat Holter and cardiac MRI were normal. Electrophysiological study done after the treatment showed no arrhythmic foci.
|Figure 4: Images (both let and right panel) of cardiac resonance imaging revealing small foci of delayed enhancing areas in the posterolateral aspect at the left ventricular outlet in the Epicardium|
Click here to view
| Discussion|| |
Sarcoidosis can affect any organ in the body. Extrapulmonary sarcoidosis may be the major manifestation and life-threatening. The prevalence of extra-pulmonary Sarcoidosis varies according to ethnicity. The predominant extra-pulmonary organ involvement different population also varies similarly and is different in different population There was more frequent involvement of the eye, liver, bone marrow, extrathoracic lymph nodes, and skin in African-Americans., Caucasians more frequently had a disorder of calcium metabolism. Japanese had higher rates of cardiac and eye involvement, while erythema nodosum lesions are most frequent in Europeans.,, Extrapulmonary sarcoidosis may be more frequent in females.
Liver is the second most common organ involvement in sarcoidosis after lungs., Fifty percent to 80% of sarcoidosis patients demonstrate granulomas on liver biopsy., The liver function test abnormalities in sarcoidosis may be as high as 35%. The most common liver function test abnormality is an elevated serum ALP. Hepatic nodules are found in <5% of patients in most series. Major clinical manifestations of hepatic sarcoidosis include granulomatous Hep, chronic cholestasis syndrome, Budd–Chiari syndrome, portal hypertension, and cirrhosis.,, Rarely, hepatic sarcoidosis may cause chronic cholestasis syndrome. Cirrhosis has been reported in 6% and portal hypertension has been estimated to occur in 3%.
The eye is the third most frequently involved organ, frequency in between 10% and 60% of patients. Granulomatous disease may cause inflammation either within the eye or in adnexal structures. Uveitis is the most common ocular manifestation of sarcoidosis.,, Involvement of the orbit and adnexal structures is less common than uveitis, occurring in 8%–27% of cases and occurs independently of uveitis. Adnexal involvement occurs in the form of lacrimal gland infiltration, formation of an orbital mass, or involvement of the lacrimal sac. The lacrimal gland is the most commonly affected adnexal site, with an estimated incidence of 5%–16%. Lacrimal gland enlargement is clinically apparent in 15%–28% of sarcoidosis patients. Optic neuropathy is a rare manifestation of sarcoidosis.
Cardiac sarcoidosis is a potentially life-threatening complication of the disease. Only 5% of patients with sarcoidosis have signs or symptoms of cardiac involvement., Granulomas may infiltrate the myocardium diffusely and extensively causing congestive heart failure. The myocardial conducting system is vulnerable to granulomas, which may result in complete atrioventricular block, premature ventricular contractions, ventricular arrhythmias, and sudden death., Cardiac involvement does not correlate with the severity of pulmonary involvement and can be difficult to diagnose in the context of active pulmonary disease. Cardiac sarcoidosis is a leading cause of death in sarcoidosis. Cardiac MRI and PET have facilitated detection of cardiac sarcoidosis. Cardiac MRI may show a pattern of late gadolinium enhancement in the basolateral area of the left ventricle, with lesions most frequently seen in the midcardial to epicardial regions. Cardiac biopsy is not practical.
The diagnosis of the isolated organ sarcoid without any other organ being involved is itself a diagnostic challenge. Tissue diagnosis with the biopsy of the organ involvement is the classic diagnosis. This was done in the first two cases, and we had ruled out the other causes and differential diagnosis. In the third case, tissue diagnosis was difficult as cardiac biopsy was not possible at our center. Thus, we relied on the imaging modality in ruling out other differentials. As cardiac sarcoid involves mid to epicardial tissue more commonly, accessibility is limited. The diagnosis of isolated cardiac sarcoid is mostly probable ruling out the other infiltrative diseases.
| Conclusion|| |
Isolated organ sarcoidosis is rare but has to be suspected and evaluated in a given clinical scenario. It needs to be diagnosed after exclusion of all the other infective and inflammatory conditions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Statement on sarcoidosis. Joint statement of the American thoracic society (ATS), the European respiratory society (ERS) and the world association of sarcoidosis and other granulomatous disorders (WASOG) adopted by the ATS board of directors and by the ERS executive committee, February 1999. Am J Respir Crit Care Med 1999;160:736-55.
Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H Jr., Bresnitz EA, et al.
Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885-9.
Design of a case control etiologic study of sarcoidosis (ACCESS). ACCESS research group. J Clin Epidemiol 1999;52:1173-86.
Pietinalho A, Ohmichi M, Hirasawa M, Hiraga Y, Löfroos AB, Selroos O, et al.
Familial sarcoidosis in Finland and Hokkaido, Japan a comparative study. Respir Med 1999;93:408-12.
Irani SK, Dobbins WO 3rd
. Hepatic granulomas: Review of 73 patients from one hospital and survey of the literature. J Clin Gastroenterol 1979;1:131-43.
Vatti R, Sharma OP. Course of asymptomatic liver involvement in sarcoidosis: Role of therapy in selected cases. Sarcoidosis Vasc Diffuse Lung Dis 1997;14:73-6.
Devaney K, Goodman ZD, Epstein MS, Zimmerman HJ, Ishak KG. Hepatic sarcoidosis. Clinicopathologic features in 100 patients. Am J Surg Pathol 1993;17:1272-80.
Herbort CP, Rao NA, Mochizuki M; Members of Scientific Committee ofFirst International Workshop on Ocular Sarcoidosis. International criteria for the diagnosis of ocular sarcoidosis: Results of the first international workshop on ocular sarcoidosis (IWOS). Ocul Immunol Inflamm 2009;17:160-9.
Ohara K, Judson MA, Baughman RP. Clinical aspects of ocular sarcoidosis. Eur Respir J Monogr 2005;10:188-209.
Bradley D, Baughman RP, Raymond L, Kaufman AH. Ocular manifestations of sarcoidosis. Semin Respir Crit Care Med 2002;23:543-8.
Demirci H, Christianson MD. Orbital and adnexal involvement in sarcoidosis: Analysis of clinical features and systemic disease in 30 cases. Am J Ophthalmol 2011;151:1074-800.
Schulte W, Kirstien D, Drent M, Costabel U. Cardiac involvement in sarcoidosis. Eur Respir J Monogr 2005;10:130-49.
Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: A clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 1978;58:1204-11.
Smedema JP, Snoep G, van Kroonenburgh MP, van Geuns RJ, Dassen WR, Gorgels AP, et al.
Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol 2005;45:1683-90.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]