Erasmus Syndrome: Association of Silicosis and Systemic Sclerosis.

Silicosis is an inflammatory disease of the lung characterized by irreversible lung fibrosis which develops from prolonged pulmonary inhalation and retention of crystalline silica and immune reaction. It mainly appears as an occupational hazard in persons involved in stone-quarrying, mining, and sand blasting. Crystalline silica is not only known to be responsible for silicosis but also for other autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)-Caplan syndrome, systemic sclerosis (SSc), and antineutrophil cytoplasmic antibody (ANCA)-related vasculitis. Erasmus syndrome is the association of silica exposure and subsequent development of SSc. The limited numbers of cases reported in the literature were miners and only sporadically involved in other professionals. Here, we report a case of a 52 -year-old stone cutter who developed silicosis and SSc after 25 years of exposure.

Introduction

Erasmus syndrome is characterized by the association of exposure to silica with or without silicosis and the subsequent development of systemic sclerosis (SSc). This syndrome is named after the doctor who first described 17 cases of SSc in gold miners [1] in South Africa in 1957. A subsequent meta-analysis of 16 studies suggested that exposure to silica is a significant risk factor in the development of SSc, particularly in males.[1] Erasmus syndrome is rarely reported from India. The index case was on treatment for diffuse cutaneous systemic sclerosis, but on considering radiological examination and occupational history, the final diagnosis of Erasmus syndrome was made.

Case Report

A 52-year-old male presented with a history of episodic bluish discoloration of fingers and toes on exposure to cold, as well as slowly progressive binding down of skin for last 1 year. There was history of finger tip ulceration and gangrenous changes. The patient also developed dyspnoea for 5 months, initially on exertion and later even at rest. He also had chest pain which was mild in intensity and localized over the bilateral upper chest, as well as arthralgia (small joints) for 4 months. There was no history of dysphagia, photosensitivity, weight loss, fever or cough. He was a stone cutter by occupation for the last 25 years. No family history of similar complaints was noted. The patient was a smoker for the last 30 years.

On examination, there was binding down of skin over the face, bilateral hands, forearms, chest, and legs (modified Rodnan score: 18/51). There was bluish pigmentation over both sides of the upper part of manubrium sterni. Bilateral hands had sclerodactyly, Raynaud's phenomenon, digital pitted scars having hyperkeratotic crust [Figure 1], and longitudinal curvature of nails with no apparent nail fold telangiectasias.

Figure 1

(a) Binding down of skin over the face, neck, and chest with appearance of salt and pepper pigmentation over chest (b) Hands showing Raynaud's phenomenon and digital pitted scars. (c) Sclerodactyly

Laboratory investigations: Normal hemogram except anemia (hemoglobin, 9.6 g%) and erythrocyte sedimentation rate of 55 mm 1st hour. Liver and renal functions and urine analysis were normal. HIV, HBV, and HCV serology was negative. ANA by indirect immunofluorescence on hep-2 cells was positive (1:640); speckled pattern; Scl-70 was also positive. Sputum for acid fast bacilli and cartridge based nucleic acid amplification test was negative. Pulmonary function tests revealed restrictive pattern.

Chest X-ray posteroanterior view: Reticulonodular opacities over the bilateral upper lobe with calcified hilar lymph nodes on the right side [Figure 2].

Figure 2

Radiological findings (a) Chest radiograph showing raticulonodular opacities over bilateral upper lobes with calcified hilar lymph nodes. (b) Axial CT showing posterior and upper lobe predominant centrilobular micronodules. (c) Axial CT image showing mediastinal and hilar lymph nodes with egg shell calcification. (d) Axial CT with mass-like consolidation over the right upper lobe

Axial computed tomography (CT) chest: There were mediastinal and hilar lymph nodes with peripheral egg shell calcification, mass-like consolidation over the posterior lobe, right upper lobe, and centrilobular micronodules, suggestive of silicosis [Figure 2].

Skin biopsy [Figure 3]: Sparse superficial and deep perivascular lymphohistiocytic infiltrate with marked thickening of collagen bundles in reticular and papillary dermis. The thickened bundles are closely packed to give a hyalinized appearance, suggestive of scleroderma.

Figure 3

Skin biopsy showing hyalinized appearance of closely packed thickened collagen bundles (H and E, ×40)

Based on occupational history, clinical examination, serology, radiological investigations, and skin biopsy, diagnosis of Erasmus syndrome (SSc in association with silicosis) was made and the patient was put on calcium channel blockers and advised to strictly stop smoking and avoid further exposure to silica and cold and referred to tertiary care centre for pulmonary medicine and rheumatology opinion before putting him on immunosuppressive treatment.

Discussion

SSc is a multisystem disorder characterized by widespread fibrotic and degenerative changes in the skin, vasculature, and internal organs. Numerous occupational and other exposures have been implicated as potential causes of SSc including silica dust,[2] epoxy resins, bleomycin, and benzene.

The frequency of occupational exposure to crystalline silica dust, as a generator of work damage, has been underestimated, even though it is recognized as a risk factor for several systemic autoimmune diseases.[3]

Majority of patients with SSc exposed to silica are males due to its occupational relevancy. So, silica may have a fundamental pathogenic role in the otherwise scarce cases of SSc among males.[4]

The association [5] of exposure to silica and development of systemic sclerosis was first analyzed by Erasmus in 1957, although credit for first observation of this association goes to Bramwel in 1914. It is established that patients with silica-associated systemic sclerosis (SA-SSc) are clinically, serologically, and immunologically indistinguishable from idiopathic SSc, even though SA-SSc patients have a higher prevalence and severe pulmonary [26] involvement (bibasilar fibrosis). Although there have been occasional reports of spontaneous remission in idiopathic SSc, no such event has been documented in silica-induced SSc.[6] Anti- Scl-70 antibodies are the predominant autoantibodies present in SA-SSc and is usually associated with severe interstitial lung disease. Perhaps in genetically susceptible people who are exposed to silica there is increased production of the anti-Scl-70 antibody.[7] Freire et al.[8] evaluated survival in SA-SSc patients and found it to be less than in the control “idiopathic” SSc group.

We suggest that silicosis should be ruled out in every patient of SSc, especially in males because lung involvement is an important aspect in the prognostic outcome and stopping the exposure to toxic agents in some cases can stabilize the progression of the disease and even lead to improvement.

Declaration of patient consent

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.