Lung, Pulmonary & Respiratory Research

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Received: January 01, 1970 | Published: ,

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Abstract

A patient was referred to general medicine clinic for evaluation of affirm, non-tender, subcutaneous, mobile nodules on the left forearm with bilateral hilar lymphadenopathy on CT chest, it was challenging to diagnose the condition and provide appropriate management to the patient. Clinical, radiological and histopathological confirmed subcutaneous sarcoidosis with extra cutaneous hilar lymph node involvement which is a rare form of nodular cutaneous sarcoidosis. There are many other aetiologies can cause granulomatous inflammation ruled out by imaging, special test and special stains and characteristic of lesion on histology. Mainstay of treatment is oral corticosteroid. Depending upon response to corticosteroid and its potential side effects due to long duration use, methotrexate can be used as steroid sparing agent which has shown good outcome in such cases.

Keywords: subcutaneous sarcoidosis, nodular sarcoidosis, epithelioid granuloma, sarcoidosis, corticosteroids, methotrexate

Introduction

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology that affects individuals worldwide and is characterized pathologically by the presence of non-caseating granulomas in involved organs and tissues.¹ Jonathan Hutchinson described the first case in 1869.² It involves skin, lung, lymph nodes, eyes, joints, brain, kidneys, and heart. Skin involvement is the second most following pulmonary sarcoidosis. Nodular Muscle involvement in sarcoidosis was first reported by Licharew in 1908. 25% patients of sarcoidosis presents with cutaneous lesions, it varies in morphologies, including papules, nodules, plaques, and infiltrated scars³ versus subcutaneous sarcoidosis occurs in 1.4 to 6 % patients of systemic sarcoidosis. Subcutaneous sarcoidosis affects women commonly, in their fifth and sixth decades. Lesions could be multiple, bilateral, asymmetrical, asymptomatic hard indurate mobile subcutaneous nodule/nodules located in upper extremities, commonly involves forearm, without any changes in overlying epidermis.⁴ Nodular muscular sarcoidosis often mimics a tumour .To rule out this confusion MRI and muscle biopsy are useful investigations.^5,6 Biopsy and histopathological examination is the gold standard method of diagnosis which shows “naked” granuloma formation which has sparse lymphocytes at margin with epithelioid cells with little or no necrosis. Diagnosis is confirmed after ruling out differentials which cause granulomatous lesion.⁷ Initial treatment option is steroid. Immunosuppressive agents have been used in corticosteroid resistant form.⁸ Here, we report the case of asymptomatic nodular sarcoidosis with pulmonary involvement showing bilateral hilar lymphadenopathy and small pulmonary nodules on imaging which was initially thought to be fibro-sarcoma.

Case report

A 61 years old man with rapidly enlarging painless mass on his left forearm which is noticed 2 months ago. It is mostly painless and initially thought to be fibro-sarcoma. There is no history of trauma. Ultrasound repeated twice, the size has increased from 14.4 x 4.7 cm to 18 x 6cm. He has had multiple sebaceous cysts removed from his back. He has background history of type II Diabetes and is on Lantus 20U nocte, Diabex 1gm BD, Diamicron MR 120mg nocte and hyperlipidaemia treated with Lipitor 40mg.He is a Diesel mechanic, a non-smoker and a social drinker. He has family history of Type II Diabetes. There was no axillary or inguinal lymphadenopathy. He has unremarkable systemic signs (Figures 1–4). CT chest has shown bilateral extensive hilar mediastinal lymphadenopathy with right upper lobe sub-pleural nodule and left lower lobe sub-pleural nodule. The distribution of hilar node did raise the possibility of sarcoidosis and lymphoma .There was no parenchymal lung involvement showing consolidation or fibrosis. Serum Angiotensin Converting Enzyme level was 100 and urine calcium excretion is 7.8.Spirometry Respiratory Function Test was suggestive of Good patient’s compliance. The flow volume loops, lung volumes and CO gas transfer are all within normal limits. His histopathology has been found to be a case of subcutaneous sarcoidosis involving muscle. As this is nodular form of muscular sarcoidosis, making it the least common subtype of specific lesion of this disease is often confused with a soft tissue neoplasm. Based on the clinical, radiological and histological findings, he was started on oral Prednisolone and has regular followed up with Respiratory Physician.

Figure 1 A firm, mobile, painless nodule, raised above skin with normal overlying epidermis.

Figure 2 US suggestive of hypoechoic oval nodule underneath skin .

Figure 3 MRI of left forearm showed intramuscular involvement with homogenous high signal intensity area.

Figure 4 CT chest has shown.

Discussion

In 1899, a Norwegian dermatologist Caesar Boeck described sarcoid skin lesion “fleshy” meaning “sakodes” in Greek. Darier-Roussy described specific subtype of nodular cutaneous in 1904. Drier-Roussy sarcoidosis is now replaced by more accurate term ‘subcutaneous sarcoidosis’.^9–11subcutaneous sarcoidosis is a nonspecific form of sarcoidosis, a non-severe systemic disease and is not associated with chronic fibrotic disease. Granuloma primarily involves subcutaneous tissue.¹² Subcutaneous sarcoidosis diagnosis is associated with extra-cutaneous systemic disease involvement, especially bilateral hilar adenopathy. It also has been described in the absence of systemic disease. Subcutaneous sarcoidosis presents as painless, firm, mobile nodules without overlying epidermal involvement.¹¹ Normally, asymptomatic muscle involvement occurs in 50-80% of sarcoidosis patients, whereas symptomatic involvement is very rare.¹³Asymptomatic involvement has been reported in the early stages of the disease. Symptomatic involvement of muscles or myopathy electromyography abnormalities have reported in chronic and usually the systemic form of, sarcoidosis.^14,15 Three different types of symptomatic muscular involvement in sarcoidosis have been reported which are nodular, acute myositis, and chronic myopathy. However, nodular form of sarcoidosis is a rare condition.⁵Clinically, it may appear single or many lesions, fleshy, deepseated, non-tender, normally appearing epidermis or hyper-pigmented nodule, tend to coalse to form linear bands.¹⁶A very few reports shown evidence of a symmetrical muscle contracture can occur sarcoidosis.¹⁷ Due to nodular nature of lesion, the differential diagnosis are giant cell tumour of tendon sheath, metastasis, foreign body granuloma, subcutaneous granuloma annulare, xanthoma, rheumatoid nodule, myxoid cyst, lipoma, erythema elevatumdiutinum, fungal or atypical mycobacterium infection, calcinosis, and gout.¹⁶ MRI is helpful in detecting intramuscular nodular sarcoidosis which evaluates the extent and distribution of underlying muscular involvement to monitor steroidal response. Axial spin-echoT 1 and T2 contrast enhanced images shows an oval nodule with a star-shaped area of low signal intensity surrounded by homogenous high signal intensity area.^18,19 Chest Radiograph findings used for staging of pulmonary sarcoidosis based on The Siltzbach classification system. Stage 0 is normal appearance at Chest X-ray; stage 1 is lymphadenopathy only; stage 2 is lymphadenopathy and parenchymal lung disease; stage 3 is parenchymal lung disease only; stage 4 is pulmonary fibrosis.²⁰High-resolution computed tomography is the most sensitive and specific imaging method for the evaluation of sarcoidosis especially in cases where atypical presentation predominates. Nodular pattern is very common which varies in size small to large cavitary lesions mimicking neoplasm. Nodules are distributed peri lymphatic region, involving the peri bronchovascular cuffs, interlobular septa, sub pleural region, centrilobular areas and the entire length of the fissures. A part from nodules, there can be parenchymal or reticular opacity. Air trapping is relatively due to granulomas or fibrosis leading to small airway disease which correlates with restrictive pattern of pulmonary function test. Bronchiectasis is uncommon form of sarcoidosis.²¹

Anaemia is uncommon but if present, it is usually anaemia of chronic disease or autoimmune haemolytic anaemia can occur.²² There can be leukopenia, eosonophilia. Elevated CRP is more associated with more severe form of chronic sarcoidosis which is under research proving better response to infliximab.^23,24 Hypercalciuria is more common. Serum ACE levels is safe, simple, non-invasive test .It is elevated in 75% patients of sarcoidosis. It is nonspecific because serum ACE levels can be elevated in other condition which mimics sarcoidosis. It relevance in clinical practice to assess response to treatment or compliance is unclear.²⁵ Histology suggests inflammatory infiltrate of sarcoid granulomas, composed of epithelioid cells with multinucleated giant cells with sparse lymphocytes limited to the hypodermis, sharply demarcated at the dermo-hypodermic junction. In low-power view, it resembles lobular panniculitis.²⁶ However, all lesions of sarcoidosis may or may not demonstrate classic findings.²⁷ Subcutaneous sarcoidosis is differentiated from erythema nodosum due to several factors with main feature of predominantly lobular rather than septal involvement.²⁸ Erythema nodosum is distinguished clinically also due to painful, red, raised and non-ulcerative subcutaneous nodules.²⁹ Management plans varies from no treatment for benign course or not cosmetically displeasing, to specific topical or systemic therapy depending upon extra-cutaneous systemic involvement. Corticosteroids is the cornerstone of cutaneous sarcoidosis.¹⁵ For most nonlife-threatening sarcoid organ involvement, starting dose of corticosteroids is 20 to 40 mg for 6 months to 2 years can be weaned to lowest effective dose to avoid potential adverse effects.

If disease is recalcitrant or patient experience side effects of corticosteroids, additional immunomodulatory agents which are steroid sparing such as methotrexate, hydroxychloroquine, azathioprine, and cyclophosphamide can be use. Methotrexate is 80% effective for skin lesions and has been well studied steroid sparing agent and relatively safe according to long term studies.²⁹ Hydroxychloroquine has been used with significant response rate in small case series of cutaneous sarcoidosis.

Subjective improvement in chronic cutaneous sarcoidosis is seen in patients who has been prescribed Thalidomide. Infliximab is used as treatment option for refractory sarcoid patients. There is little data exist to guide therapy for cytotoxic (i.e, mycophenolate and leflunomide) and biological agents (i.e, rituximab, adalimumab and abatacept) are likely to be tried in chronic sarcoidosis.²⁹

Conclusion

Sarcoidosis is a multisystem granulomatous disorder which can present as numerous skin manifestations such as cutaneous nodule. It mimic infections and malignancies. There is various differential diagnoses for this condition. Understanding and applying the process of diagnostic reasoning is important to make sure not to miss serious diagnosis. A variety of therapies have been used for cutaneous sarcoidosis. Therapy should be used to derive therapeutic decisions which maximize patient benefit and acceptance. However, high quality evidence to support the efficacy of these treatments is limited. This article helps physician, being an educator by recognizing the importance of this rare case in the wider community to develop skills to undertake this role as after good understanding of patient with his illness.