Erasmus Syndrome: Silicosis and Systemic Sclerosis.

Several occupational hazards, especially exposure to silica, have been implicated as causal factors for the development of scleroderma-like disorders. Compared to other connective tissue disorders, silica-associated systemic sclerosis (SA-SS) is relatively rare. Silica-induced scleroderma is indistinguishable from idiopathic systemic sclerosis. However, the former expresses a high predisposition of pulmonary involvement and anti-Scl-70 antibody. We report the case of a 42-year-old male, stone cutter by occupation, who was diagnosed as simple chronic silicosis and developed systemic sclerosis.

INTRODUCTION

Silicosis is a fibrosing disease of the lung caused by inhalation, retention, and pulmonary reaction to crystalline silica, exposure to which occurs as an occupational hazard in quarrying, mining, masonry, and sand blasting. Systemic sclerosis (SS) has been defined as a generalized disorder of small arteries, microvessels, and diffuse connective tissue, and is characterized by scarring and vascular obliteration in the skin, gastrointestinal tract, lung, heart, and kidney. Its etiology is not fully understood, though many occupational exposures are implicated such as vinyl chloride, epoxy benzene, organic solvent, and less commonly, silica exposure.[1] Compared to other connective tissue disorders, silica-associated systemic sclerosis (SA-SS) is relatively rare. To our knowledge, three cases have been reported in India till now.

CASE HISTORY

A 42-year-old male presented with progressive dyspnea on exertion since 6 month, swelling of legs since 4 month, cough with minimal expectoration and fever since 1 month. The patient also complained of tightening of the skin of hands, feet, face, back, and chest for the last 4 months. There was also associated generalized joint pain and bluish discoloration of fingers on exposure to cold. There was no history of dysphagia, hemoptysis, chest pain, loss of appetite, and loss of weight. Patient had not taken any antitubercular treatment previously. He had no history of hypertension and diabetes mellitus. He was a nonalcoholic and nonsmoker. He worked as a stone cutter in the mining industry for the past 15 years.

On general physical examination, there was limitation of opening of mouth (microcheily). Cutaneous examination revealed extensive thickening of skin over the face, dorsum of hands, forearm, chest, back, and legs [Figure 1]. Skin over the chest and back was shiny and tight and there was loss of wrinkles on forehead. There were pitted scar at finger tips on both hands [Figure 2]. Joints of the hand, wrist, and knee were tender. Digital clubbing was present. No abnormal findings were detected on respiratory system examination. Complete blood count, liver function test, and renal function test were normal. HIV was nonreactive, and the patient was euglycemic. There was no hematuria and albuminuria. Serum C reactive protein (CRP) and rheumatoid factor was negative. Sputum Ziehl-neelsen stain was negative. Skiagram chest PA view showed q (1.5-3mm) nodules over middle and lower lung zones bilaterally [Figure 3].

Figure 1

Tight and shiny skin over the neck, arms, and chest

Figure 2

Pitted scar at finger tips on both hands

Figure 3

X-ray of the chest showing bilateral nodular opacity over the mid and lower lung zones

Two-dimensional echo revealed no evidence of pulmonary hypertension. Upper gastrointestinal endoscopy was normal. Fibreoptic bronchoscopy revealed normal tracheobronchial tree. No Mycobacteria grew on bactec culture performed on bronchoalveolar lavage. Spirometry showed restrictive pattern (FVC-37% with normal FEV1%). High-resolution computed tomography of the chest showed randomly distributed nodules in both lungs [Figure 4]. Antinuclear antibody (ANA) was found to be positive. Scl-70 antibody titre specific for systemic sclerosis were 123.03 units (>80 strong positive). On detailed clinical, radiological, and immunological evaluation together with prolonged history of stone cutting, the case was diagnosed as simple chronic silicosis with SS.

Figure 4

High-resolution computed tomography of the chest showing multiple randomly distributed nodules in both lungs

DISCUSSION

Few case reports have documented the co-existence of silicosis and progressive systemic sclerosis (PSS). In 1914, Bramwel first reported an association between scleroderma and occupations associated with silica exposure.[2] In 1957, Erasmus described an apparently high prevalence of PSS in gold miners exposed to dust containing a high percentage (±30%) of free silica compared with a large male nonmining hospital population.[3] Rodnan et al. also noted that, of the 60 male patients diagnosed to be suffering from PSS in the period of 1955–1956, 26 were exposed to prolonged and heavy exposure to silica dust.[4]

Devulder et al. discussed the association and presented bibliography up to 1977.[5] They suggested that the eponym “Erasmus syndrome” be used when referring to the co-existence of silicosis and PSS. The first case of silicosis-induced systemic sclerosis in India was reported by Khanna et al. in 1997.[6] Other two cases were reported by Bainara and Arya and Ganguly et al. in 2013.[78]

Chronic exposure to silica causes alterations in soluble interleukin-2 (IL-2) receptors in affected patients. Increased lymphokines either stimulate collagen production or other cells such as monocyte or mast cells to release factors that in turn induce collagen biosynthesis in fibroblasts. This is supported by the fact that increased levels of soluble IL-2 receptors are found in systemic sclerosis. Silica can activate monocyte to release cytokine IL-1, 6, and TNF alpha which are fibroblast proliferative factor, which increases the production of collagen leading to cutaneous sclerosis, vascular occlusion, and pulmonary fibrosis.[9] SS has also been seen in cases of short intense exposure (5–10 years), i.e., patients with accelerated silicosis are more prone to autoimmune disease.

SS is characterized by three major processes – disease-specific autoantibodies, organ fibrosis, and small vessel vasculopathy. There is a female preponderance in 30–50 years age group. Patients can be classified into two principal subsets defined largely by the pattern of skin involvement as well as clinical and laboratory manifestations. Diffuse cutaneous SSc is associated with progressive skin induration, starting in the fingers and ascending from the distal to proximal extremities, the face, and the trunk. These patients are at a risk of early pulmonary fibrosis and acute renal involvement. Patients with limited cutaneous form of systemic sclerosis (lcSSc) generally have long-standing Raynaud's phenomenon before other manifestations of SSc appear. Skin involvement in lcSSc is slowly progressive and remains limited to the fingers (sclerodactyly), distal extremities and face, but the trunk is not affected.[10] Other affected organs include lung, gastrointestinal tract, kidney, musculoskeletal system, and heart.

No drug significantly influences the natural course of SSc overall, but various drugs are of value in treating organ-specific symptoms. Penicillamine is used for treating skin thickening for a long time. Calcium channel blockers, such as nifedipine 20 mg po tid or as an extended-release formulation, may help Raynaud phenomenon but may worsen gastric reflux. Bosentan, sildenafil, tadalafil, and vardenafil are other alternatives for severe Raynaud phenomenon.

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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.