|Year : 2022 | Volume
| Issue : 4 | Page : 285-288
Erasmus syndrome: A case series of rare co-occurrence of silicosis and systemic sclerosis
VM Jaanakhi, Batoee Ram, Mohammad Javed Qureshi, Manisha Jain, Sumeet Sawale
Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan, India
|Date of Submission||29-Dec-2021|
|Date of Acceptance||05-Feb-2022|
|Date of Web Publication||24-Dec-2022|
Dr. Manisha Jain
E-182, Shiv Park, Ambabari, Jaipur, Rajasthan - 302 039
Source of Support: None, Conflict of Interest: None
Erasmus syndrome is the association of silica exposure and subsequent development of systemic sclerosis. Here we discuss five cases that presented with progressive shortness of breath, arthralgia, skin tightening, and Raynaud's phenomenon. History of exposure to silica dust was present in all cases, and further serological (Anti-Scl-70 antibody positive), radiological, and histopathological (skin biopsy) investigations confirmed the diagnosis of systemic sclerosis. Hence the diagnosis of Erasmus syndrome was made. Therefore, careful screening should be done in patients of silicosis with systemic symptoms to rule out any associated connective tissue disorder. Timely diagnosis and early intervention can prevent the patients from developing life-threatening complications and improved quality of life.
Keywords: Anti-Scl-70 antibody, Erasmus syndrome, Raynauds phenomenon, silicosis, systemic sclerosis
|How to cite this article:|
Jaanakhi V M, Ram B, Qureshi MJ, Jain M, Sawale S. Erasmus syndrome: A case series of rare co-occurrence of silicosis and systemic sclerosis. Indian J Occup Environ Med 2022;26:285-8
|How to cite this URL:|
Jaanakhi V M, Ram B, Qureshi MJ, Jain M, Sawale S. Erasmus syndrome: A case series of rare co-occurrence of silicosis and systemic sclerosis. Indian J Occup Environ Med [serial online] 2022 [cited 2023 Apr 1];26:285-8. Available from: https://www.ijoem.com/text.asp?2022/26/4/285/364937
| Introduction|| |
Systemic sclerosis (SS) is an autoimmune disease that involves small arteries, micro-vessels and diffuse connective tissue, and is characterized by scarring and vascular obliteration in the skin and internal organs. Although pathology has been elucidated in recent studies, exact pathogenesis is still enigmatic. Environmental and occupational exposures have been implicated in some studies, namely vinyl chloride, epoxy benzene, organic solvent, and, rarely, silica.
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. The association of previous exposure to silica and later development of systemic sclerosis (SS) was first analyzed by Erasmus in 1957 and is known as Erasmus syndrome. Silica-associated systemic sclerosis (SA-SS) is a rare entity as only few case reports are available in literature. To our knowledge, this is the first case series of Erasmus syndrome in India.
| Case History|| |
A 32-year-old non-smoker male presented with history of progressive shortness of breath for the last three years, low-grade fever, right-sided chest pain for three months, along with loss of weight and appetite. He also gave history of progressive skin tightening, mainly over the extremities involving the small joints of the upper and lower limb (metacarpo-phalangeal and inter-phalangeal joints). The patient had bluish discoloration of hands upon exposure to cold, suggestive of Raynaud's phenomenon. He had no history of dysphagia and joint pain. The patient was a stone crusher by occupation with a seven-year history of silica dust exposure. On examination, clubbing was present along with skin fixity leading to apparent clawing, skin thickening, and ulcers over hands [Figure 2]a and elbow. Respiratory system examination revealed tachypnea, decreased chest movements, dull percussion note and reduced breath sounds on right infrascapular and infra-axillary areas. Other system examinations were found to be normal.
|Figure 1: Chest skiagram and CT thorax of patients with Erasmus syndrome. From top left, (a and b) case 1 and (c-f) of cases 2–5 respectively|
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|Figure 2: Visible skin changes in hands of patients with Erasmus syndrome. From top left, (a-e) of cases 1–5 respectively|
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Chest X-ray PA view showed right-sided pleural effusion with heterogenous opacity in left upper and lower zones [Figure 1]a. Routine blood investigations were normal. Diagnostic thoracocentesis was done and it was straw in colour with lymphocyte predominance (95%), exudative (Protein 4.40), sugar 86 mg/dl, and ADA 75. Sputum smear was negative for acid-fast bacilli. CECT thorax showed fibrocavitatory lesion in left upper lobe and areas of fibrotic bands, scarring, and calcification with pleural thickening in left upper and lower lobes [Figure 1]b. Tree-in-bud opacities, miliary nodules in bilateral lung parenchyma, right pleural effusion, and multiple enlarged lymph nodes were also present. Skin punch biopsy was inconclusive. Antinuclear antibody, anti-scl-70 was strongly positive and anti-centromere antibody was negative. Two-dimensional echocardiography (2D-ECHO) showed no evidence of pulmonary hypertension. Pulmonary function test (PFT) showed restrictive ventilatory defect. Hence the diagnosis of pulmonary tuberculosis with Erasmus syndrome was made. Patient was put on anti-tubercular therapy, Bronchodilators, analgesics and referred to the Rheumatology department for further management.
A 39-year-old male patient who was a chronic smoker presented to our department with complaints of progressive worsening of shortness of breath, dry cough, and bilateral diffuse chest pain from two months. He also complained of bluish discoloration of hands upon exposure to cold, tightening of the skin of his hands for the last four years, arthralgia for two years, and high-grade fever for ten days. He worked as a stone crusher for 10 years, and quit from that occupation last nine years prior.
On examination, pallor and clubbing were present. Thickening and pigmentation of skin on the hands was also noted [Figure 2]b. HRCT chest revealed early conglomerated fibrotic masses with multiple small 1–3 mm rounded airspace nodules in upper zone of both lungs [Figure 1]c. Multiple enlarged lymph nodes were also present. PFT revealed restrictive ventilatory defect. 2D-ECHO revealed pulmonary hypertension. The laboratory tests were as follows: hemoglobin was 9.8 g/dL; total leukocyte count was 18800/mm3; and was positive for anti-scl-70 antibody. Skin punch biopsy taken from the right hand showed collagenization of subcutaneous tissue with presence of eccrine glands between collagen bundles suggestive of scleroderma. Correlating the history of prolonged exposure to silica dust, positive serological markers, consistent radiological and histopathological features, a final diagnosis of Erasmus syndrome was made. Patient was treated with higher antibiotics, bronchodilators, and referred to a rheumatologist for further management.
A 33-year-old male patient who was an active smoker presented to our OPD with chief complaints of progressive shortness of breath and dry cough for two years. He also had history of arthralgia, generalized skin tightening for one-and-a-half years, and bluish discoloration of nail beds on exposure to cold for one year. Patient had no other comorbidities. He was a stone grinder in the mining industry for 15 years.
On general examination, clubbing, skin ulcers, and clawing were evident on hands [Figure 2]c. Respiratory system examination was unremarkable. Routine blood investigations were within normal range. HRCT thorax revealed multiple small centrilobular nodules [Figure 1]d with large fibrotic masses with irregular margins, calcifications and bronchiectasis predominantly in bilateral upper lobes. Few enlarged calcified lymph nodes were also present. Anti-Scl-70 and anticentromere antibodies were found to be negative. Morphology in skin punch biopsy showed thick, hypocellular collagen bundles and eccrine glands were present higher up in the dermis in favour of systemic sclerosis. PFT showed restrictive ventilatory defect. 2D-ECHO was found to be normal. Hence the diagnosis of Erasmus syndrome was made, and patient was started on treatment as per rheumatology consultation.
A 38-year-old non-smoker male patient presented to the OPD with progressive exertional dyspnea and productive cough for three months, small joints pain for two-and-a-half months and bluish discoloration of hands on cold exposure. He was an active stone cutter for the past 17 years.
On general examination, skin tightening was seen in both hands [Figure 2]d. Respiratory system examination revealed bilateral fine basal crackles. Routine blood investigations were within normal limits. HRCT thorax showed multiple tiny discrete random nodules in bilateral lung parenchyma along with ground glass opacities and septal thickening predominantly in bilateral lower lung lobes [Figure 1]e. Complete immune profile was done where Anti-Scl-70 was strongly positive and Sm and AMA-M2 was borderline positive. Further skin punch biopsy was done and showed hyperkeratosis, hypergranulosis, and mild spongiosis in epidermis, and extensive dermal fibrosis with perivascular and periadnexal lymphocytic infiltration was also present. Pulmonary function tests done suggested restrictive ventilatory defect. Six-minute walk test showed a 6MWD of 310 meters, but the patient desaturated from 97% to 92%. 2D-ECHO showed evidence of pulmonary hypertension. Hence a diagnosis of Erasmus syndrome was made. Patient was started on symptomatic treatment and immunosuppressives as per rheumatology consultation.
A 38-year-old non-smoker male presented with history of progressive shortness of breath for last three years, low-grade fever, and bilateral diffuse chest pain for two months. He also gave history of progressive skin tightening mainly over the chest and extremities involving the small joints of the upper and lower limb. He had no history of Raynaud's phenomenon, dysphagia, and joint pain. The patient was a tile setter by occupation with five years of silica dust exposure. Patient had vitals of SpO2 85% on room air, RR of 20 breaths/min, HR of 110/min, and BP of110/80 mm Hg. On examination, skin thickening was present over hands [Figure 2]e, forearm, and anterior chest wall. Other system examinations were found to be normal.
Chest X-ray PA view showed heterogenous opacity in bilateral upper zones. Routine blood investigations were normal. CECT thorax showed conglomerated fibrotic masses in bilateral upper lobe with multiple military nodules [Figure 1]f. Multiple enlarged lymph nodes with dense internal calcifications were also seen. Skin punch biopsy on right hand showed the presence of mononuclear perivascular infiltrates and myofibroblasts. Anti-Scl-70 was weakly positive and anticentromere antibody was negative. 2D-ECHO showed minimal pericardial effusion and no evidence of pulmonary hypertension. PFT could not be performed. Hence Erasmus syndrome was diagnosed. Patient was put on oxygen supplementation, symptomatics, and referred to a rheumatologist for further management.
| Discussion|| |
Silicosis is an inflammatory disease of the lung that is characterized by irreversible lung fibrosis, which develops from prolonged pulmonary inhalation and retention of crystalline silica, and immune reaction mounted by the body to this extraneous chemical.
Silicosis is often associated with the development of other diseases, such as pulmonary tuberculosis, lung carcinoma and less commonly, autoimmune diseases like systemic sclerosis (SSc), rheumatoid arthritis, and systemic lupus erythematosus. Immune system dysfunction is well described in association with silicosis, including increased prevalence of circulating immune complexes as well as increased production of serum auto-antibodies, such as antinuclear antibody and RF.
Systemic sclerosis is a chronic inflammatory disease characterized by three cardinal pathophysiologic processes: 1) diffuse microangiopathy; 2) inflammation and autoimmunity; and 3) visceral and vascular fibrosis in multiple organs.
SSc patients can be classified into two principal subsets
- Diffuse cutaneous SSc (progressive skin induration with multisystem involvement early in the course of the disease);
- limited cutaneous form of systemic sclerosis (lcSSc) (Skin involvement limited to the fingers (sclerodactyly), distal extremities and face. Other system involvement is infrequent and late.)
There is evidence of the association of SSc with occupational and environmental factors. In 1957, Erasmus reported cases of SSc in gold miners in South Africa, who had been exposed to silica powder. Erasmus syndrome is, by definition, characterized by the association of exposure to silica, with or without silicosis, and the subsequent development of SSc.
Crystals of silica of less than 1 micrometer are phagocytosed by macrophages and are transported to the regional lymph nodes. The mechanism of the association of exposure to silica. SSc seems to involve the systemic inflammatory response triggered by silica after phagocytosis and release of mediators such as IL-1, 6, and TNF alpha by activated alveolar macrophage. The cytokines released are fibroblast proliferative factor, which increases the production of collagen leading to cutaneous sclerosis, vascular occlusion, and pulmonary fibrosis.
Silica also appears to activate humoral immunity in a dysregulated manner via IL-1 release which stimulates T-helper cells to activate B cells for auto-antibody production. Alterations in soluble interleukin-2 (IL-2) receptors may also play a role.,
In our case series, all Erasmus syndrome cases identified were male, belonged to the age group of 30–40 years, and resided in the northeastern part of Rajasthan, similar to a case reported by S Jain et al. The mean exposure time was 14.5 years (4–33 years) in one study. Silicosis has also been seen in cases of short intense exposure (5–10 years), that is, patients with accelerated silicosis are more prone to developing autoimmune disease. Similarly, four of our patients were exposed to silica dust for <10 years while the other one had >15 years exposure history.
Patients with lcSSc generally have long-standing Raynaud's phenomenon before other manifestations of SSc appear. In our case series, four patients had history of Raynaud's phenomenon except for one. Anti-Scl-70 and anti- RNA polymerase III antibodies are characteristic of diffuse cutaneous SSc, whereas anticentromere antibody is characteristic of lcSSc. Anti-Scl-70 was found positive in four of our patients.
Positive skin punch biopsy findings further favored the diagnosis of systemic sclerosis in four out of five patients. The patients showed a restrictive pulmonary pattern, which can be present in both SSc and silicosis. In patients with SSc, PAH carries an extremely poor prognosis and accounts for 30% of deaths. Out of five, two of our patients had evidence of pulmonary hypertension.
Management of Erasmus syndrome depends on the extent of multi-organ involvement. Treatment options include corticosteroids, immunosuppressive agents, antifibrotic therapy, vascular therapy (calcium channel blockers, phosphodiesterase 5 inhibitors, endothelin 1 receptor antagonist), skin care, etc.
| Conclusion|| |
Erasmus syndrome is a rare entity. Hence careful screening should be done in patients of silicosis with systemic symptoms to rule out any associated connective tissue disorder. Timely diagnosis and early intervention can prevent the patients from developing life threatening complications, and improve their quality of life.
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Conflicts of interest
There are no conflicts of interest.
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