Systemic sclerosis: environmental and occupational risk factors

There is growing concern about the association between systemic sclerosis and certain environmental and occupational risk factors, including exposures to vinyl chloride, adulterated cooking oils, L-tryptophan, silica, silicone breast implants, organic solvents, and other agents such as epoxy resins, pesticides, and hand/arm vibration. This article highlights the current medical research that has examined these associations in scleroderma-like disorders and in systemic sclerosis.     

Systemic sclerosis

Systemic sclerosis (SSc) presents with a great deal of variability from patient to patient and classification and subset criteria will be analysed and discussed. SSc has been reported in people from all over the world. The prevalence and incidence, however, varies from country to country and within the same country in different ethnic groups. These differences will be elucidated. Genetic and environmental factors associated with the disease will be discussed.SSc is predominantly a female disease, with the female:male ratio ranging from 3:1 to 8:1 and being higher in childbearing years. Progenitor cells acquired during pregnancy have been suggested to play a role by inducing a graft-versus-host disease (microchimerism). Recent epidemiological studies on the relationship between SSc and previous pregnancies will be discussed. SSc is associated with a significant morbidity and mortality. Survival has improved in the last 15 years. Factors associated with such improvement will be analysed.     

Systemic sclerosis

Systemic sclerosis is a disease characterized by several distinctive features. This disease spares children, and its incidence increases steadily with age. Women are affected more than men, especially during childbearing years. Although there is no overall racial predilection, SSc occurs most frequently and severely in young black women. Family and genetic studies suggest only a weak genetic predisposition, but there are many occupational agents that may be implicated in the pathogenesis. The disease with its involvement in many organ systems results in a significant reduction in lifespan. Improvement in survival of renal crisis has been dramatic with the use of ACE inhibitors. Further epidemiologic studies using subsets of patients with more homogeneous clinical and laboratory features will lead to a better understanding of this complex disease.     

Systemic sclerosis

Systemic sclerosis (SSc; syn. systemic scleroderma) is a rare autoimmune disorder with characteristic cutaneous manifestations. Prevalence in women is fivefold higher than in men. The course of the disease is slowly progressive with a variable degree of internal organ involvement due to fibrosis and obliteration of small vessels. The diffuse form shows more frequent and severe organ manifestations compared to the limited form. Increased mortality is particularly related to a cardiopulmonary involvement leading to a 5-year survival of around 75%. Treatment indications are dependent on the severity of the disease. In the acute state, immunosuppressive agents are needed in case of significant organ involvement. Vasodilative drugs are often used for the symptomatic treatment of Raynaud's phenomenon.     

Systemic sclerosis and occupational risk factors: role of solvents and cleaning products

OBJECTIVE: To analyze occupational and non-occupational exposure factors suspected of being associated with scleroderma (SSc), with a view to inculpating or excluding certain potentially toxic substances (e.g., solvents), thereby contributing to the recognition of such toxins in the field of occupational health. METHODS: The study comprised 10 men and 83 women diagnosed with SSc between 1995 and 1999 (American College of Rheumatology criteria) and early SSc, and 206 age and sex matched controls. The SSc registry is all-inclusive in the French administrative departments of Isere and Savoie so controls were randomly selected from the general population (using telephone directories) in these departments to ensure full representation. Exposure factors were analyzed for each subject by a personal questionnaire, and an individual evaluation was carried out by an industrial expert. Data were analyzed by conditional logistical regression adjusting for educational level. RESULTS: Construction workers were at significantly higher risk of contracting SSc; odds ratio (OR) = 4.01 (95% confidence interval 1.14-14.09). Analysis by industrial experts identified exposure to certain toxic substances regularly used by these same workers as risk factors for SSc: cleaning products: OR = 1.66 (0.90-3.08) (both sexes) and OR = 1.71 (0.92-3.20) (women only); solvents: OR = 3.23 (1.58-6.63) (both sexes) and OR = 2.80 (1.28-6.11) (women only); synthetic adhesives: OR 25.36 (1.36-472.28) (on 3 exposed cases). CONCLUSION: Exposure to either cleaning products or solvents emerged as a risk factor for SSc. Exposure factors should be characterized and results of all studies compared to implement appropriate preventive measures in relevant workplaces.     

Systemic sclerosis associated with cutaneous exposure to solvent: case report and review of the literature

Sclerodermatous skin changes and systemic sclerosis have been reported to occur as a result of contact with several different organic solvents. We describe a 41-year-old man who developed systemic sclerosis after working for 15 years in a foundry, where he had extensive cutaneous contact with multiple organic solvents (trichloroethane, xylene, trimethylbenzene, and naphthalene). Cutaneous exposure to organic solvents may be a factor in the etiology of some cases of systemic sclerosis.     

Systemic sclerosis in men

PURPOSE: To study the initial clinical features and describe the outcome of systemic sclerosis in a cohort of French men. METHODS: Patients with systemic sclerosis based on Leroy's criteria were included. In this retrospective study we compared a cohort of men to a cohort of women, diagnosed between 1997 and 2005 in departments of internal medicine and rheumatology. RESULTS: One hundred and twenty-one patients were included amongst which thirty-six men. The mean follow-up duration was 6.5 years. The time to diagnosis was significantly shorter in men than in women. Diffuse cutaneous systemic sclerosis, cutaneous ulcers and interstitial syndrome on chest radiograph were more frequent at diagnosis in men than in women. An environmental factor (silica) was observed in only nine men. During the follow-up, incidence of restrictive lung disease was significantly higher in men than in women (37% versus 14% p=0.01) with higher rates of oxygen dependency (22% versus 5% p<0.01). Cumulated survival rates in men were 92% at 5 years, 72% at ten years and 43% at 15 years, respectively. The mean survival was 13 years in men (IC 95%: 10-16) versus 23 years in women (IC 95%: 10-36) with no statistical difference (p=0.27). CONCLUSION: If interstitial and restrictive lung disease, oxygen dependency and diffuse systemic sclerosis were more frequent in men than in women, this data did not provide any evidence of survival difference between men and women with systemic sclerosis.     

Systemic sclerosis and pregnancy

PURPOSE: Pregnancy in a patient with systemic sclerosis (SSc) may pose a double problem to the medical team: influence of SSc on pregnancy and consequences of pregnancy to SSc manifestations. CURRENT KNOWLEDGE AND KEY POINTS: Concepts have evolved. SSc was considered for a long time not only as not very propitious for pregnancy but also as a strict contraindication for procreation because risks for the mother and the baby were thought to be major. Currently, fertility is thought to be normal. Miscarriages and small-for-gestation age infants rate do not seem to be higher in SSc. Maternal and perinatal mortality is also not higher in SSc without severe visceral manifestations, i.e. without either pulmonary hypertension, or cardiac or respiratory insufficiency. Conversely, there is a significantly higher frequency of premature infants in SSc. As regards influence of pregnancy on SSc, the greatest fear is the occurrence of renal crisis, which may be life threatening for both mother and child. Each elevation of blood pressure, even if this increase is mild, should be considered as potentially very serious. However, pregnancy itself does not seem to increase the risk of renal crisis. Consequences of pregnancy to SSc manifestations are various but usually mild. FUTURE PROSPECTS AND PROJECTS: SSc is not a strict contraindication for pregnancy only if severe organ involvement, diffuse subset of SSc or recent onset of the disease has been ruled out. Physicians should be aware of specific problems, which SSc is possibly posing during pregnancy. Finally, it has been recently suggested that pregnancies could be involved in the pathogenesis of SSc through persisting microchimerism of fetal origin.     

Systemic sclerosis in childhood

Juvenile systemic sclerosis (jSSc) is a rare disease of childhood, and the amount of published data is limited. It appears that its clinical presentation differs from adult disease and the limited form affects only very few children. The organ involvement pattern differs also from the adult form. Prognosis seems to be better with a 5-yr survival of 95% of the jSSc patients. The validation of the outcome measures for children with jSSc is currently in progress. Regarding effective treatment, there are no paediatric data and the paediatric rheumatologist needs to rely on the experiences in adult disease.     

Toxic hepatitis in occupational exposure to solvents

The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work.     

Perspectives on occupational exposure to antineoplastic drugs

This review has attempted to focus on the salient features of the potential risks of occupational exposure to the major antineoplastic agents that have broad utility in cancer chemotherapy, as well as in the treatment of a spectrum of refractory non-malignant conditions. An initial focus centered about the classes (primarily alkylating agents, antimitotics, antibiotics, and antimetabolites), types of action and their carcinogenicity, genotoxicity, and reproductive effects exhibited by many of these agents in animals and treated patients. Nurses, pharmacists, and oncologists are the principal individuals with a potential risk to these agents primarily during the preparation and administration of these agents. Although the number at potential risk are not known precisely, they are believed to be relatively small in the aggregate, perhaps numbering several thousand. The measurement of exposure has generally been attempted on a relatively small number of nurses and pharmacists by biological monitoring employing urinary mutagenicity assays and cytogenetic analysis with conflicting results. The levels of exposure currently found are low compared to the therapeutic doses employed and are probably much lower than that which may have occurred earlier before the employment of vertical laminar flow hoods and the more recent implementation of guidelines and/or recommendations. The long-term effects of exposure to occupational personnel at potential risk of exposure to chemotherapeutic agents and waste are not known. Although studies to date have failed to show conclusively that nurses and pharmacists are at risk to the carcinogenic, genotoxic and reproductive effects of these agents, prudence would dictate that every effort be taken to minimize their exposure during the handling and disposal of antineoplastic drugs.