Sarcoidosis presenting as a loss of weight with preserved appetite

Abstract

Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology affecting a wide range of organs and is characterised by the presence of noncaseating granulomas. It has rarely been reported in Sri Lanka. This case describes a 36-year-old male presenting with a loss of weight despite a preserved appetite. He had evidence of sarcoidosis with pulmonary, lymph node, eye, hepatosplenomegaly, thyroid and parotid gland involvement with hypercalcaemia. He was successfully treated with glucocorticoids.

Introduction

Sarcoidosis is a multisystemic inflammatory disease with a wide range of clinical manifestations. The first description of sarcoidosis is by British surgeon and dermatologist Jonathan Hutchinson in the late 1800s. ¹ It is considered a rare disease in Sri Lanka, with the first case of sarcoidosis reported in 2002. ² We present a case of a 36-year-old male who presented with loss of weight and was found to have sarcoidosis with multisystem involvement.

Case

A 36-year-old previously healthy male presented with loss of weight for 5 months despite a preserved appetite with his weight reducing from 80 kg to 67 kg. His caloric intake and physical activity level were constant. He had a history of episodic dry cough for 1 year. There was no evening pyrexia or night sweats, and he did not have a past or contact history of tuberculosis. He had an episode of a left-side painful red eye 2 months before admission. He also complained of intermittent bilateral painless facial swelling episodes over the past year. He had no chronic diarrhoea or steatorrhea but complained of constipation. He did not have heat intolerance, excessive sweating or palpitations but complained of polyuria and polydipsia. He was a non-smoker and a social drinker. He chewed Betel for the last 3 years. Betel nut chewing is a practice seen in South Asia where areca nuts are chewed together with betel leaves and slaked lime for their stimulant and narcotic effects. His drug and family history was not significant. He worked as a carpenter and had possible occupational exposure to wood dust, mould, and chemicals such as paint and solvents.

On examination, he was not pale or icteric. He had a body mass index (BMI) of 22 kg/m². He had no features of nutrition deficiency and had no rashes. There was a palpable non-tender cervical lymph node on the left side. There were no other palpable nodes. He had no goitre and no parotid swelling. He had a respiratory rate of 12/min, the trachea was central and on auscultation, lungs were clear with equal air entry. Abdomen examination revealed mild hepatomegaly. Cardiovascular, nervous and musculoskeletal system examinations were normal. An ophthalmologic examination revealed evidence of old anterior uveitis in the left eye.

His initial investigations are summarised in Table 1. Significant hypercalcaemia was noted.

Table 1.

Investigations.

Investigation	Result	Reference range
White cell count (/L)	5.97 × 109	4–10
Haemoglobin (g/dL)	14.1	12–16
Platelets (/L)	196 × 109	150–400
C-reactive protein (mg/dL)	8.6	<5
Erythrocyte sedimentation rate (mm/1st hour)	45
Creatinine (μmol/L)	120.6	74–110
Urea (mmol/L)	3	2.8–7.2
Sodium (mmol/L)	137.9	135–145
Potassium (mmol/L)	3.9	3.5–5.1
Aspartate aminotransferase (U/L)	19.3	<50
Alanine transaminase (U/L)	18.1	<50
Alkaline phosphatase (U/L)	119.4	40–150
Total protein (g/L)	78.95	66–83
Albumin (g/L)	38.9	35–52
Serum calcium (mmol/L)	3.64	2.02–2.6
Thyroid stimulating hormone (μIU/nL)	1.32	0.55–4.78

Abnormal investigations are in bold.

Chest x-ray showed bilateral hilar lymphadenopathy. High-resolution computed tomography (HRCT) Chest revealed bilateral symmetrical hilar and mediastinal lymphadenopathy with normal lung fields (Figure 1). Sputum for acid-fast bacilli was negative and the Mantoux test was normal. Ultrasound of the abdomen showed mild hepatosplenomegaly. Electrocardiogram and 2D echocardiography were normal. Ultrasound of the neck revealed multiple left-sided cervical lymphadenopathy with altered architecture, a focal hypoechoic area in the thyroid gland suggestive of focal thyroiditis and patchy areas of hypoechoic areas in bilateral parotid glands suggestive of chronic parotitis. Cervical lymph node biopsy revealed non-caseating granulomatous lymphadenitis favouring sarcoidosis. The focal thyroiditis and parotitis are also probably due to sarcoidosis infiltration. However, biopsies of the lesions were not done. Due to affordability issues, the serum angiotensin-converting enzyme levels could not be performed.

Figure 1.

HRCT chest showing bilateral hilar lymphadenopathy.

The patient was started on prednisolone 30 mg daily and was continued for 4 weeks. The serum calcium levels were normal at 4 weeks. Prednisolone was tapered gradually to a maintenance dose of 10 mg daily. At 6 months of follow-up, the patient’s calcium levels remained within normal levels with prednisolone, and he was asymptomatic. No adverse reactions were reported with the treatment and the patient was compliant with treatment.

Discussion

Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology affecting a wide range of organs, mainly the lungs, skin, eyes or lymphatic system and is characterised by the presence of noncaseating granulomas. ¹ It is prevalent throughout the world with the highest incidence in Scandinavian countries. ³ The mean age of onset is from 30 to 55 years with the age of onset lower in males. There is a slight female predominance. ⁴ Pathogenesis involves a dysregulated immune response to environmental exposure in a genetically susceptible host. Occupational and environmental factors such as inorganic particles, insecticides and mouldy environments are thought to play a role in the development of sarcoidosis. ¹

The clinical manifestation of sarcoidosis is highly variable with the involvement of any organ system. According to A Case Control Etiologic Study of Sarcoidosis, organ involvement in decreasing order of frequency are lungs (95%), skin (15.9%), lymph node (15.2%), eye (11.8%), liver (11.5%), erythema nodosum (8.3%), spleen (6.7%), neurologic (4.6%), parotid/salivary gland (3.9%), bone marrow (3.9%), calcium (3.7%), ENT (3%), cardiac (2.3%), renal (0.7%), bone/joint (0.5%) and muscle (0.4%). ⁵ Löfgren’s syndrome refers to the triad of erythema nodosum, bilateral hilar adenopathy and polyarthralgia or polyarthritis often with fever. ¹ Heerfordt’s syndrome refers to parotid swelling, uveitis and facial nerve palsy. ⁵ Lung involvement can be classified as follows based on radiographic characteristics. ⁶

• Stage I – Bilateral hilar lymphadenopathy

• Stage II – Bilateral hilar lymphadenopathy and parenchymal infiltration

• Stage III – Parenchymal infiltration without hilar adenopathy in regular chest radiography

• Stage IV – Advanced fibrosis with severe distortion of the normal lung architecture predominately in the middle and upper lobes with evidence of bronchiectasis, hilar retraction, bulla, cysts and more rarely honeycombing.

The thyroid gland can be involved rarely in sarcoidosis. Ultrasound scan shows scattered nodular shadows (1–3 cm) and irregular hypoechoic areas suggestive of granulomas. Fluorodeoxy glucose-positron emission tomography (FDG-PET) and core needle biopsy can be used to confirm the diagnosis. ⁷ Parotid gland involvement is a well-known complication of sarcoidosis. Bilateral painless parotid swelling is a common presentation. ⁸ Ultrasound findings can be nonspecific and range from nodal enlargement to diffuse or partial parotid gland involvement with varying degrees of echogenicity and vascularity. ⁹

Sarcoidosis can have numerous cutaneous manifestations. These include papules, patches that may become hypopigmented, subcutaneous nodules, plaques, lupus pernio, scarring alopecia, ulcers, ichthyosiform lesions and erythema nodosum. ¹⁰ However, our patient did not have any evidence of cutaneous sarcoidosis.

Our patient presented with a loss of weight despite a preserved appetite. Examination and investigation revealed lung (stage I, bilateral hilar lymphadenopathy), lymph node (cervical and mediastinal), eye (anterior uveitis), hepatosplenomegaly, parotid gland (chronic parotitis) and thyroid gland (focal thyroiditis) involvement. In addition, he had hypercalcaemia. Such a presentation with constitutional symptoms and multisystem involvement is more commonly seen with tuberculosis in Sri Lanka where the disease is endemic. Sarcoidosis is rarely reported. ² The presence of noncaseating granulomas with a negative Mantoux test and sputum for acid-fast bacilli (AFB) helped to confirm the diagnosis of sarcoidosis in our patient. ¹¹

According to the American Thoracic Society Guidelines, the diagnosis of sarcoidosis is based on three major criteria, namely, a compatible clinical presentation, the presence of non-necrotising granulomatous inflammation in one or more tissue samples and the exclusion of alternative causes of granulomatous disease. ¹² The clinical features that are highly probable of a diagnosis of sarcoidosis include Lofgren’s syndrome, lupus pernio, uveitis, optic neuritis, erythema nodosum, bilateral hilar adenopathy and hypercalcaemia. ¹² Although sarcoidosis can be diagnosed in most cases by identifying the characteristic non-caveating and non-necrotizing granulomas, histology is not always pathognomonic. Hypersensitivity pneumonitis, berylliosis, granulomatosis with polyangiitis, fungal infections, tuberculosis, foreign body granuloma, drugs and malignancies can have similar histopathological features to sarcoidosis. A multidisciplinary assessment approach based on clinical, laboratory, radiological and histological evaluation would be useful in such instances. ¹³ FDG-PET is useful in assessing organ-specific disease activity as well as identifying responses to treatment and relapse. ¹⁴ However, in resource-limited settings as in Sri Lanka the ability to perform investigations to rule out other differential diagnoses is limited. Hence, a high level of suspicion of sarcoidosis should be maintained and the clinical presentation and biopsy plays an important role in diagnosis.

Comorbidities are common in sarcoidosis and cause variability in the presentation of the disease and increase the complexity of diagnosis. They are mostly seen involving the lungs and heart. Pulmonary hypertension, pulmonary fibrosis, chronic pulmonary aspergillosis and obstructive sleep apnoea are a few pulmonary comorbidities. Comorbid cardiovascular disease risk is increased in sarcoidosis. Autoimmune diseases, lymphoproliferative malignancies, type 2 diabetes and thyroid disease are also possibly associated with sarcoidosis. ¹⁵

Although most cases of sarcoidosis resolve spontaneously, the risk of organ dysfunction and hypercalcaemia as seen in our patient requires treatment. First-line treatment is with glucocorticoids with an initial dose of 20–40 mg per day which is tapered to 5–15 mg per day after 1–3 months if there is a clinical response. ¹⁶ Second-line treatment includes methotrexate, azathioprine, leflunomide and mycophenolate. Hydroxychloroquine is used in cutaneous disease, hypercalcaemia and neurosarcoidosis. Third-line options include TNF-α inhibitors such as infliximab and adalimumab. ¹ Lung, liver and heart transplantation has also been performed in patients with severe end-organ damage. ¹⁶

Conclusion

Sarcoidosis should be considered as a differential diagnosis in a patient presenting with a loss of weight. Thorough screening should be done to assess organ involvement. Prompt treatment with glucocorticoids should be initiated if there is severe disease or hypercalcaemia.