Sarcoidosis Beyond the Lungs: A Rare Case of Splenic Involvement

INTRODUCTION

Sarcoidosis is a multisystem inflammatory condition that can affect multiple organs, and splenic involvement, though uncommon, may present with symptoms such as significant weight loss, loss of appetite, generalised weakness, and maculopapular skin lesions. The disease involves an inflammatory response in a genetically susceptible host. Clinical presentations range from asymptomatic to organ failure, including skin lesions like maculopapular lesions, erythema nodosum, and lupus pernio, ocular manifestations like uveitis, and neurological involvement such as facial nerve paralysis. Cutaneous sarcoidosis occurs in around 10% of cases in India.

Diagnosis of sarcoidosis is often made by excluding other causes like infections or environmental exposures, and the presence of noncaseating granulomas characterises it. The pathological hallmark of sarcoidosis is granuloma formation. Imaging, such as roentgenograms, is key for detecting pulmonary involvement. Scadding staging system is used to assess the extent of hilar lymphadenopathy and lung infiltrates. Prognosis varies widely; some patients experience remission, while others have a more chronic disease course that can persist for decades.

In rare cases involving the spleen, treatment typically targets controlling systemic inflammation and preventing organ damage. These cases often require long-term monitoring due to the risk of chronic progression. Herein, we present a rare case of splenic involvement in sarcoidosis in a 50-year-old diabetic, hypertensive, and hypothyroid female who presented with a history of significant weight loss, loss of appetite, generalised weakness, and maculopapular lesions over both upper limbs. This case of sarcoidosis with splenic involvement illustrates the varied presentation of the disease.

CASE REPORT

A 50-year old female with comorbidities of diabetes, hypertension, and hypothyroidism reported with complaints of generalised weakness, significant weight loss, decreased appetite, and bilateral knee and ankle joint pain in the past 6 months. She also complained of fever with upper respiratory symptoms such as dry cough, chest pain, breathlessness on exertion (MMRC Grade 2), swelling over the neck, and maculopapular lesions over bilateral upper limbs in the past 1 month [Figure 1]. The patient had no history of palpitations, orthopnea, or paroxysmal nocturnal dyspnoea. There was no history of deleterious habits and biomass exposure. On examination, the patient was afebrile with a pulse rate of 72 bpm, blood pressure of 120/80 mmHg in the supine position, respiratory rate of 20 cycles/min, saturation of 98% at room air, and there were palpable lymph nodes(1.5×1 cm) over the bilateral cervical, axillary, and inguinal areas. Per abdominal examination revealed hepatosplenomegaly. The rest of the systemic examination, including the cardiovascular, central nervous, and musculoskeletal systems, was unremarkable.

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Figure 1:

Shows maculopapular lesions over (a) the left arm (black arrow) and (b) the right forearm (black arrow).

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A complete hemogram showed microcytic hypochromic anaemia with no other abnormal findings, thereby reducing the likelihood of lymphoma [Table 1]. Renal function test showed hypokalemia [Table 2]. Liver function test showed elevated alkaline phosphatase levels [Table 1]. The electrocardiogram showed a normal sinus rhythm. Chest X-ray revealed bilateral hilar lymphadenopathy [Figure 2]. Two-dimensional echocardiography (2D-ECHO) showed normal valves and chambers with an ejection fraction of 60% and with no regional wall motion abnormality. Mantoux test showed no induration. TB QuantiFERON gold test was negative, making tuberculosis unlikely. Ultrasonography (USG) guided biopsy of the left inguinal lymph node, which measured 2×1 cm, was performed. Histopathological examination of the biopsy tissue showed multiple epithelioid cell non-caseating granulomas mixed with giant cells with no evidence of necrosis or malignancy [Figure 3]. USG-guided fine-needle aspiration cytology (US-guided FNAC) of the right cervical lymph node was suggestive of granulomatous lymphadenitis. Ziehl Neelsen stain for acid-fast bacilli, Gomori methenamine stain, and periodic acid Schiff stain in the lymph node were negative. Serum Antinuclear antibody (ANA) was negative, making autoimmune and connective tissue aetiologies unlikely.

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Figure 2:

Chest X-ray, PA view showed bilateral hilar lymphadenopathy (black arrows).

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Figure 3:

Non-caseating granulomas from inguinal lymph node biopsy (black arrows). H&E, 400x magnification (40x objective).

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Serum calcium levels were elevated (11.5 mg/dL), and serum angiotensin-converting enzyme (ACE) levels were >120 [Table 2]. A 24 h urinary calcium level was 13.5 mg/dL. Skin biopsy was taken from the maculopapular lesions over the upper limb, and it showed a noncaseating granuloma with an asteroid body [Figure 4]. USG abdomen and pelvis showed hepatosplenomegaly. Computed tomography (CT) of the thorax showed hepatomegaly with multiple enhancing lesions in both lobes [Figure 5]; Computed tomography of the abdomen revealed a prominent spleen with multiple poorly enhancing lesions [Figure 6], multiple enlarged lymph nodes in the mediastinum, bilateral axillae, paraaortic, aortocaval, and bilateral inguinal locations. Fundus examination was unremarkable.

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Figure 4:

Skin biopsy showed asteroid body (black arrows). H&E, 400x magnification (40x objective).

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Figure 5:

Computed tomography of the thorax showed enlarged mediastinal lymph nodes (white arrows).

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Figure 6:

Computed tomography of the abdomen showed multiple enhancing lesions in the spleen and liver (black arrows).

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Symptomatic treatment was initially administered to the patient. Upon confirmation of the non-caseating nature of the granuloma through biopsy, oral steroids were commenced, resulting in a notable improvement in the patient’s condition. Given the chronicity of the disease and its disseminated involvement in the lungs, skin, liver, and spleen, the patient was then prescribed Methotrexate along with folic acid supplementation. Following this course of treatment, the patient improved symptomatically and was discharged with instructions for regular follow-up.

DISCUSSION

Sarcoidosis is a multisystem disorder characterised by granulomas, with the pulmonary system being most commonly affected. The cause of sarcoidosis remains unknown. Initial presentation in about 30% of patients includes extrapulmonary involvement such as the skin, eyes, heart, kidneys, musculoskeletal system, central nervous system, and reticuloendothelial system.^[1] Females more commonly experience skin and ocular issues, while males tend to exhibit cardiac findings.^[2]

More than 90% of individuals with sarcoidosis experience pulmonary issues, showcasing symptoms such as cough, dyspnoea, and chest pain.^[3] Concurrently, they may encounter weight loss, fatigue, fever, and night sweats.^[4] The staging of a patient’s chest radiograph is valuable for gauging the severity of sarcoidosis and predicting the likelihood of spontaneous remission among those with similar disease severity.^[5]

Cutaneous involvement arises in around 25% of sarcoidosis cases, often presenting as asymptomatic nodules or papules with several described variants. The impact of sarcoidosis on the eyes and cardiovascular system remains uncertain.^[6] Hepatic involvement is relatively common, with 50% to 65% of patients exhibiting liver granulomas, which are more prevalent in the African and American populations. Most individuals with hepatic involvement are asymptomatic, displaying liver enlargement and biochemical abnormalities, notably elevated alkaline phosphatase, as evident in our case.

The prevalence of splenomegaly varies, with one study citing 6% through physical examination and another indicating over 30% through imaging.^[6] Splenic involvement can lead to anaemia, leukopenia, and thrombocytopenia. Extrapulmonary symptoms extend to the kidney and electrolyte abnormalities. Calcium metabolism defects, stemming from extrarenal calcitriol production by activated macrophages, may result in hypercalcemia. If left untreated, this condition can lead to chronic renal failure due to renal calcium deposits.

To diagnose sarcoidosis, other conditions must be ruled out, and confirmation comes through histopathologic evidence of noncaseating granulomas, coupled with clinical and radiographic signs of sarcoidosis manifestations.^[7] These granulomas are typically found in the alveolar septa and along the lymphatic routes of the bronchioles and pulmonary vasculature. They develop from a chronic inflammatory response involving monocytes, lymphocytes, macrophages, and fibroblasts. Notably, the majority of granulomas resolve without leaving scars or lasting effects.

Laboratory findings may encompass leukopenia, increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, elevated serum alkaline phosphatase (ALP) levels, and a rise in ACE levels. However, serum ACE elevation lacks diagnostic precision due to low sensitivity and specificity. Anaemia is uncommon but can result from chronic disease or splenic involvement. High-resolution CT (HRCT) is typically favoured for follow-up assessments, revealing parenchymal changes in mid- to upper lobes, including bronchovascular bundle thickening, nodules along bronchi and vessels, subpleural nodules, bronchial wall thickening, parenchymal bands, fibrosis, and cysts. Additional imaging, like fluorine-18 fluorodeoxyglucose positron emission tomography and radiotracer scanning, may uncover hidden lesions or inflammatory sites.^[8] Pulmonary function tests (PFTs) are valuable in assessing sarcoidosis’s impact on lung parenchyma, often indicating abnormal results with a restrictive pattern and reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in most patients.^[9]

Acute presentation of sarcoidosis has no treatment. In relapsing or refractory cases, steroids remain the mainstay, and depending upon the need, sparing immunosuppressive agents like methotrexate, azathioprine, hydroxychloroquine, and leflunomide can be considered. In resistant cases, biological therapies like anti-tumour necrosis factor (anti-TNF) alpha agents such as Infliximab or Adalimumab can be used. In chronic cases of sarcoidosis, we follow a similar pattern of treatment. We started the patient initially on symptomatic treatment. Oral steroids were commenced after confirmation through biopsy. Methotrexate with folic acid supplementation was initiated due to chronicity and the disseminated nature of the disease. The patient improved symptomatically and was discharged with instructions for regular follow-up.

CONCLUSION

Sarcoidosis is primarily diagnosed through a process of exclusion. Papular lesions represent a classical manifestation of cutaneous sarcoidosis. Liver and splenic involvement are typically infrequent but were evident in this particular case. The cornerstone in diagnosing sarcoidosis lies in histopathological evidence. Prompt identification of sarcoidosis is crucial, as it often goes undetected and untreated. Commencing with steroids, followed by a gradual tapering regimen and the inclusion of immunosuppressive agents or anti-TNF alpha agents based on the disease duration, response, and extent of involvement, can significantly benefit the patient and enhance the prognosis.