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Review
Sarcoidosis: the links between epidemiology and aetiology Simon Dubrey,1 Shreena Shah,2 Timothy Hardman,3 Rakesh Sharma4 1
Department of Cardiology, Hillingdon Hospital, Uxbridge, Middlesex, UK 2 The Medical Admissions Unit, Queens Hospital, Romford, Essex, UK 3 Niche Science & Technology Ltd., Unit 26, Richmond-UponThames, London, UK 4 Department of Cardiology, The Royal Brompton Hospital, London, UK Correspondence to Dr Simon W Dubrey, Department of Cardiology, Hillingdon Hospital, Pield Heath Road, Uxbridge, Middlesex UB8 3NN, UK; [email protected] Received 14 January 2014 Revised 30 August 2014 Accepted 1 September 2014
ABSTRACT Sarcoidosis is a multisystem inflammatory disease, the aetiology of which has still to be resolved. The proposed mechanism is that a susceptible genotype is exposed to one or more potential antigens. A sustained inflammatory response follows, which ultimately results in pathognomonic granuloma formation. Various clinical phenotypes exist with specific genetic associations influencing disease susceptibility, protection, and clinical progression. Occupational and environmental factors, including microbial elements, may then effect the development of this disease. Sarcoidosis is a heterogeneous disease, showing geographic and racial variation in clinical presentation. It demonstrates a familial tendency and clear genotype associations. Additionally, it appears to cluster within closely associated populations (eg, work colleagues) and appears to be related to selected occupations and environmental exposures. Frequently occult, but occasionally fatal, this disease has a very variable prognosis. It is also unusual in having no specific biomarker. The epidemiology and multiple factors that appear to influence the aetiology of sarcoidosis illustrate why this disease state is frequently described as a clinical enigma.
INTRODUCTION
To cite: Dubrey S, Shah S, Hardman T, et al. Postgrad Med J 2014;90:582–589. 582
Since sarcoidosis was first reported, the search continues for an aetiology, a biological marker and specific cure for this disease. Attention has shifted to a more genetic orientated approach, but researchers continue to argue the case for infective, environmental and occupational factors. Sarcoidosis is a multisystem inflammatory disease in which noncaseating granulomas form in almost any organ or tissue (figure 1). The exposures and occupations shown in figure 2 indicate the vast range of factors proposed as influencing the aetiology of this disease. From the outset sarcoidosis is an unusual condition; many patients are unaware they have the disease with the majority recovering spontaneously and without treatment. For a smaller, but significant, proportion of patients there can be devastating and, on occasions, fatal consequences. Despite agreement that the condition is influenced by a variety of genetic and environmental interactions, many questions remain unanswered. These questions, with no specific ‘cure’, or biomarker of disease presence, means sarcoidosis has frequently been designated an ‘enigma’.1–4 We describe the epidemiology and aetiology of sarcoidosis and expand on reasons why this disease continues to confound the medical profession.
EPIDEMIOLOGY Human sarcoidosis is recognised to occur worldwide, although large regional variations in prevalence exist. In Europe, Caucasians are more commonly affected than other races and western Europeans more than eastern Europeans. Scandinavia, particularly Sweden, has a high prevalence of 64 per 100 000 population (incidence of 19 per 100 000/year).5 UK estimates, reported in 1992, are
Review
Sarcoidosis: the links between epidemiology and aetiology Simon Dubrey,1 Shreena Shah,2 Timothy Hardman,3 Rakesh Sharma4 1
Department of Cardiology, Hillingdon Hospital, Uxbridge, Middlesex, UK 2 The Medical Admissions Unit, Queens Hospital, Romford, Essex, UK 3 Niche Science & Technology Ltd., Unit 26, Richmond-UponThames, London, UK 4 Department of Cardiology, The Royal Brompton Hospital, London, UK Correspondence to Dr Simon W Dubrey, Department of Cardiology, Hillingdon Hospital, Pield Heath Road, Uxbridge, Middlesex UB8 3NN, UK; [email protected] Received 14 January 2014 Revised 30 August 2014 Accepted 1 September 2014
ABSTRACT Sarcoidosis is a multisystem inflammatory disease, the aetiology of which has still to be resolved. The proposed mechanism is that a susceptible genotype is exposed to one or more potential antigens. A sustained inflammatory response follows, which ultimately results in pathognomonic granuloma formation. Various clinical phenotypes exist with specific genetic associations influencing disease susceptibility, protection, and clinical progression. Occupational and environmental factors, including microbial elements, may then effect the development of this disease. Sarcoidosis is a heterogeneous disease, showing geographic and racial variation in clinical presentation. It demonstrates a familial tendency and clear genotype associations. Additionally, it appears to cluster within closely associated populations (eg, work colleagues) and appears to be related to selected occupations and environmental exposures. Frequently occult, but occasionally fatal, this disease has a very variable prognosis. It is also unusual in having no specific biomarker. The epidemiology and multiple factors that appear to influence the aetiology of sarcoidosis illustrate why this disease state is frequently described as a clinical enigma.
INTRODUCTION
To cite: Dubrey S, Shah S, Hardman T, et al. Postgrad Med J 2014;90:582–589. 582
Since sarcoidosis was first reported, the search continues for an aetiology, a biological marker and specific cure for this disease. Attention has shifted to a more genetic orientated approach, but researchers continue to argue the case for infective, environmental and occupational factors. Sarcoidosis is a multisystem inflammatory disease in which noncaseating granulomas form in almost any organ or tissue (figure 1). The exposures and occupations shown in figure 2 indicate the vast range of factors proposed as influencing the aetiology of this disease. From the outset sarcoidosis is an unusual condition; many patients are unaware they have the disease with the majority recovering spontaneously and without treatment. For a smaller, but significant, proportion of patients there can be devastating and, on occasions, fatal consequences. Despite agreement that the condition is influenced by a variety of genetic and environmental interactions, many questions remain unanswered. These questions, with no specific ‘cure’, or biomarker of disease presence, means sarcoidosis has frequently been designated an ‘enigma’.1–4 We describe the epidemiology and aetiology of sarcoidosis and expand on reasons why this disease continues to confound the medical profession.
EPIDEMIOLOGY Human sarcoidosis is recognised to occur worldwide, although large regional variations in prevalence exist. In Europe, Caucasians are more commonly affected than other races and western Europeans more than eastern Europeans. Scandinavia, particularly Sweden, has a high prevalence of 64 per 100 000 population (incidence of 19 per 100 000/year).5 UK estimates, reported in 1992, are
