European Respiratory Society

A wide range of acute and chronic pulmonary disorders are capable of diffusely affecting the lung parenchyma with variable amounts of inflammation and fibrosis. A variety of agents and clinical conditions have been associated with interstitial lung disorders. Sarcoidosis is one of the most common causes of idiopathic interstitial lung disease. Clinical presentation can range from asymptomatic to severe respiratory symptoms. Sarcoidosis is considered as a multisystemic disease and chest physicians are frequently involved in the evaluation and management of this disease. The treatment of sarcoidosis ranges from nothing to complex immunosuppressive agents. Given the range of effective therapies for sarcoidosis, appropriate treatment is important. This issue of the European Respiratory Monograph provides the reader with the current status of our understanding of sarcoidosis. Different aspects of the multisystem involvement of this disease condition are discussed by experts in the field of sarcoidosis. Their contributions offer the reader new insights, ideas and perspectives in the management of sarcoidosis.

  • European Respiratory Society Monographs
  1. Page viii
  2. Page ix
  3. Page 1
    Correspondence: O.P. Sharma, Room 11-900, Los Angeles County-University of Southern California Medical Center, 1200 North State Street, Los Angeles, CA 90033, USA. Fax: 1 3232262738; E-mail:

    More than a century ago, J. Hutchinson, a surgeon-dermatologist, identified the first case of sarcoidosis at King’s College Hospital (London, UK). In the decades before and following the turn of the nineteenth century, several publications independently drew attention to what is now regarded as sarcoidosis. This trend gained a significant momentum in the latter part of the twentieth century and has continued relentlessly into the nascent years of the twenty-first century. This brief account provides a working definition of the disease and outlines the countries, institutions and individuals that have participated in the historical journey of sarcoidosis to the present.

  4. Page 13
    Correspondence: M. Thomeer, Dienst Longziekten, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium. Fax: 32 22564890; E-mail:

    The global incidence and prevalence of sarcoidosis varies between studies, mostly because of selection bias when ascertaining the actual extent of sarcoidosis in a given community. The prevalence of sarcoidosis varies between 0.03–640 per 100,000 in various studies.

    In general, the prognosis of sarcoidosis is favourable. A large percentage of affected individuals may never manifest clinical disease and up to 30% have spontaneous remission. A chronic course occurs in 10–30% of patients, at times resulting in a significant impairment of lung function. Mortality rates of 1–6% have been reported.

    Studies that defined possible environmental, occupational and genetic risk factors as a cause of sarcoidosis are promising. Most of the research in defining risk factors for sarcoidosis are still in the early stages and only a few robust case-control studies exist, of which A Case Control Etiologic Study of Sarcoidosis (ACCESS) attracted the most attention.

  5. Page 23
    Correspondence: L.S. Newman, Division of Environmental and Occupational Health Sciences, Dept of Medicine, National Jewish Medical and Research Center, 1400 Jackson St, Room G212, Denver, Colorado 80206, USA. Fax: 1 3033981983; E-mail:

    The cause or causes of sarcoidosis remain unknown. This chapter addresses some of the reasons for the collective ignorance, discusses clues that can be derived from past research literature, reviews the strengths and weaknesses of the prevailing candidates, including microbes, and proposes a conceptual framework for addressing causation.

    With increasing numbers of studies supporting a putative role for biological agents in sarcoidosis pathogenesis, this review critically examines the body of evidence toward the goal of making reviews, such as this one, someday seem quaint and obsolete.

  6. Page 49
    Correspondence: G. Semenzato, Università di Padova, Dipartimento di Medicina Clinica e Sperimentale, Immunologia Clinica, Via Giustiniani 2, 35128 Padova, Italy. Fax: 39 0498754179; E-mail:

    By influencing many of the physiological properties of immunocompetent cells, including proliferation, differentiation, activation and chemotaxis, chemokines and cytokines act as critical mediators of cell function and cell-to-cell communication in sarcoidosis. In fact, it is well established that the release of a cascade of interacting extracellular signalling proteins orchestrates the trafficking of immune cells during sarcoid inflammatory process. Cytokines regulate the expression of adhesion molecules on the lung vascular endothelium within and around the site of inflammation by combining with relevant receptors on neighbouring cells. This in turn favours the entrance and activation of type-1 T-helper (Th) cells, and modulates the local survival and proliferation of different types of immune cells, including macrophages, which in turn release pro-inflammatory cytokines. As a result, cytokines with pro-inflammatory destructive biological functions set the stage for the development of irreversible remodelling of the lung tissue, the evolution toward pulmonary granuloma formation, and, in some sarcoid individuals, the development of fibrosis.

  7. Page 64
    Correspondence: R.M. du Bois, Interstitial Lung Disease Unit, Dept of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, SW3 6LR, UK. Fax: 44 2073518336; E-mail:

    Although sarcoidosis is described in almost all populations around the world, there are wide variations in the incidence and prevalence of the different clinical phenotypes, suggesting genetic influence on disease susceptibility and phenotype. It has emerged from multiple family and case-control studies that sarcoidosis does indeed have a significant genetic susceptibility. This review sets out to outline the genetic studies to date and to highlight key genetic targets and the importance of precise phenotyping.

    Despite the study of many logical (and occasionally illogical) loci, the overwhelming consensus is that the Class II major histocompatability complex (MHC) region of chromosome 6 is the major association hot spot. In this regard, Löfgren’s syndrome has been strongly associated with an extended MHC haplotype encompassing alleles in human leukocyte antigen (HLA)-DQ, HLA-DR and tumour necrosis factor, suggesting that other clinical subtypes and phenotypes might be associated with different susceptibility genes. In more global sarcoidosis, there is a consistency evolving from studies around the world that there is a small set of susceptibility HLA-DR alleles and other alleles that confer protection, possibly in association with an independent effect from the butyrophilin-like 2 gene.

    Other case-control studies using the candidate gene approach have reported some, generally less convincing, associations with genes encoding for cytokines, chemokines and infection susceptibility genes. Of these, the chemokine receptor associations are most promising.

    The development of tighter definitions of clinical phenotypes and the emergence of larger cohort studies of sarcoidosis, including familial sarcoidosis, should combine with new technological advances to build a clearer picture of the genetics of sarcoidosis susceptibility and phenotypes in the future.

  8. Page 82
    Correspondence: V. Poletti, Dept of Diseases of the Thorax, U.O. di Pneumologia Interventistica, Ospedale GB Morgagni, Via Forlanini 34, 47100 Forli, Italy. Fax: 39 0543735882; E-mail:

    Sarcoidosis is a chronic, multisystemic disorder of unknown cause characterised in involved organs by an accumulation of activated CD4+ T-cells and macrophages, noncaseating epithelioid cell granuloma, and tissue injury. The diagnosis is established when clinico-radiological findings are supported by histological evidence of noncaseating epithelioid cell granulomas. Granulomas of known causes and local sarcoid reactions must be excluded.

  9. Page 92
    Correspondence: J. De Vries, Tilburg University, Medical Psychology, Dept of Psychology and Health, P.O. Box 90153, 5000 LE Tilburg, The Netherlands. Fax: 31 134772370; E-mail:

    Fatigue still seems an underestimated problem in sarcoidosis. Objective clinical parameters are not related to fatigue. General inflammation and metabolic derangement, pain, sleeping disorders, small fibre neuropathy and depression have been postulated as possible causes. Since fatigue cannot be assessed using objective measures, validated questionnaires, such as the Fatigue Assessment Scale, are recommended for establishing the extent of fatigue. No effective treatment for fatigue in sarcoidosis is known. Case reports have shown a positive effect of anti-tumour necrosis factor-α on fatigue.

    Nonspecific symptoms, such as fatigue, have a negative impact on the quality of life and health status of sarcoidosis patients. Quality of life is particularly impaired with respect to mobility, working capacity and the activities of daily living. As long as there is no effective treatment for fatigue in sarcoidosis, rehabilitation for improvement of physical fitness, coping and self-management should be considered for some patients. Finally, it must be stressed that fatigue should be taken seriously in the management of sarcoidosis patients.

  10. Page 105
    Correspondence: J.P. Lynch 3rd, The David Geffen School of Medicine at the University of California, Division of Pulmonary, Critical Care Medicine, and Hospitalists, 10833 Le Conte Ave, 37-131 CHS, Los Angeles, CA 90095, USA. Fax: 1 3102068622; E-mail:

    Sarcoidosis is a multi-systemic inflammatory disorder, but affects the lungs in ∼90% of cases. Nonproductive cough, dyspnoea and chest pain are the most common features of pulmonary sarcoidosis.

    The diagnosis of pulmonary sarcoidosis is suggested by bilateral hilar lymphadenopathy, with or without parenchymal changes, on chest radiographs, and is supported by noncaseating granulomata in tissue biopsies. Radiographic staging of pulmonary sarcoidosis, as well as clinical and laboratory findings can be prognostic.

    Treatment of pulmonary sarcoidosis typically includes corticosteroids, but other therapeutic agents may have benefit, and treatment needs to be individualised. Lung transplantation remains a viable therapeutic alternative for patients who do not respond to pharmaceutical agents.

  11. Page 130
    Correspondence: U. Costabel, Dept of Pneumology/Allergy, Tüschener Weg 40, Ruhrlandklinik, D-45239 Essen, Germany. Fax: 49 2014334029; E-mail:

    Clinically evident cardiac sarcoidosis is noted in 2–10% of patients, although occult involvement is much higher. The involvement of the heart is an important prognostic factor in sarcoidosis. Early treatment, predominantly with corticosteroids, prevents irreversible damage of the heart and seems to be associated with good prognosis.

    Technical progress has led to improvements and new diagnostic techniques that allow a better assessment of the structure and function of the heart. However, for early diagnosis there is still no single diagnostic tool with acceptable reliability. A histological confirmation is rarely obtained, and the diagnosis is, therefore, a challenge and dependent on clinical rules. The most decisive approach is to suspect the disease and to introduce, in good time, further investigations according to the clinical presentation, e.g. cardiac arrhythmias in young patients.

    Specific therapy is long term, often lifelong, and is based on corticosteroids with or without immunosuppressants. The symptomatic treatment of cardiac arrhythmias and dysfunction corresponds to experience with dilated cardiomyopathy.

    The indication and timing of implantable defibrillators and transplantation still raises many questions.

  12. Page 150
    Correspondence: A. Eklund, Dept of Respiratory Medicine and Allergology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Fax: 46 8312705; E-mail:

    Noncaseating epithelioid cell granulomas characterising sarcoidosis may affect most organs, including the skin. Skin lesions may be the only manifestations, or just one of several other organ involvements. Roughly 25% of all sarcoidosis patients may suffer from skin lesions during the course of their disease.

    Erythema nodosum, which usually occurs at acute onset of the disease, is not characterised by granulomas and normally spontaneously resolves within weeks or months. In contrast, other skin manifestations may signal a protracted disease course. Particularly, lupus pernio may result in disfiguring lesions in the face with destruction of underlying cartilage and bone. In between these two extremes, several other types of lesions have been reported, such as red-brownish plaque formations, maculopapular eruptions, subcutaneous nodules and cicatricial manifestations. There is also a psoriasiform and an ichthyosiform of the disease.

    The therapeutic approach is similar to other manifestations of sarcoidosis. The choice of drugs depends on the severity and prognosis of the lesion and whether there is any accompanying organ involvement(s).

  13. Page 164
    Correspondence: O.P. Sharma, Room 11-900, LAC+USC Medical Center, 1200 North State Street, Los Angeles, CA 90033, USA. Fax: 1 3232262728; E-mail:

    The nervous system is involved in 5–15% of patients with sarcoidosis. When present, neurosarcoidosis can be serious and devastating. The disease presents in many different ways and resembles many other neurological disorders. Thus, without biopsy evidence, the diagnosis of nervous system sarcoidosis remains a troublesome clinical dilemma. The firm diagnosis of neurosarcoidosis requires a biopsy specimen and consistent neurological presentation in a patient with multisystemic sarcoidosis. Corticosteroids represent the drug of first choice. In addition, several cytotoxic agents and antimalarial agents are used to treat sarcoidosis. The future is pregnant with expectations of new drugs that block inflammatory cytokines involved in the pathogenesis of sarcoidosis.

  14. Page 188
    Correspondence: K. Ohara, Kichijoji Minamicho Eye Clinic, 1F, 2-4-12 Minamicho, Kichijoji, Musashino-Shi, Tokyo 180-0003, Japan. Fax: 81 0422720504; E-mail:

    Ocular involvement is seen in a significant number of patients with sarcoidosis. Involvement is more common in Japanese patients, where over half the sarcoidosis patients have ocular disease. In Europe, up to one-third of patients may be affected.

    Since eye disease may be silent, a detailed examination of the eye is strongly recommended on all sarcoidosis patients. The most common ocular manifestation is uveitis, but any portion of the eye may be affected.

    In some cases, inflammation can be controlled by local therapy usually topical steroids. When systemic therapy is needed, corticosteroids are usually effective. However, the ocular toxicity of corticosteroids includes glaucoma and cataract formation. For chronic ocular disease, there has been interest in use of methotrexate and other cytotoxic agents.

  15. Page 210
    Correspondence: T.L.Th.A. Jansen, Medical Centre Leeuwarden, Dept of Rheumatology, POB 888, 8901 BR Leeuwarden, The Netherlands. E-mail:

    Sarcoidosis is a granulomatous systemic disease potentially involving the locomotor system. The most common presentation is acute sarcoidosis in Löfgren’s syndrome. Alternative manifestations include chronic articular involvement, synovial and tendinous involvement, muscular complications, and bone involvement, such as dactylitis, pelvic pathology, skull abnormalities and spinal problems. Systemic involvements may reflect coexistent autoimmune disease and disturbed calcium metabolism resulting in osteopenia or osteoporosis.

    Corticosteroids are commonly used to treat more serious cases, but may result in additional risks of osteoporosis, which may currently be counteracted by bisphosphonates. Modern treatment options seem to be efficacious in chronic sarcoid inflammation due to the ability to block tumour necrosis factor. However, further studies are needed, specifically in the field of locomotor presentations of sarcoidosis.

  16. Page 220
    Correspondence: O.P. Sharma, Room 11-900, Los Angeles County-University of Southern California Medical Center, 1200 North State Street, Los Angeles, CA 90033, USA. Fax: 1 3232262728; E-mail:

    The classic renal lesion of sarcoidosis is an epithelioid cell granuloma. Distinction from other diseases that may cause granulomas in the kidney, particularly renal neoplasm, can be difficult. Sarcoidosis can directly involve various structures in the kidneys, causing granulomatous nephritis, nongranulomatous nephritis and vasculitis. Therefore, the firm and final diagnosis of renal sarcoidosis depends on tissue biopsy and a clinical picture consistent with multisystemic sarcoidosis. Once the diagnosis is established, therapy includes corticosteroids, antimalarial drugs and immunosuppressive agents. Hypercalcaemia rarely causes renal failure; hypercalciuria, however, is associated with a high incidence of nephrocalcinosis. Hypercalciuria is more frequent than hypercalcaemia and may be present without hypercalcaemia, but the reverse is not true. Hypercalcaemia is always associated with hypercalciuria. Abnormalities of calcium metabolism in sarcoidosis are due to increased production of 1,25-dihydroxyvitamin D3 (calcitriol) by sarcoid granulomas and activated macrophages.

  17. Page 233
    Correspondence: D.R. Moller, Division of Pulmonary and Critical Care Medicine, Dept of Medicine, The Johns Hopkins University, 5501 Hopkins Bayview Circle, Rm. 4B63, Baltimore, MD 21224, USA. E-mail:

    Although most sarcoidosis patients develop manifestations within a clinical framework typical for sarcoidosis, a small number of patients develop unusual manifestations that challenge clinicians to diagnose and establish treatment for these problems. These rare manifestations are usually the result of either an uncommon pattern of systemic involvement or granulomatous inflammation developing in an unusual location for sarcoidosis. Despite being rarely seen, these clinical manifestations reflect the same underlying pathophysiological mechanisms and clinical behaviour common to more easily recognisable systemic sarcoidosis. Similarly, the known T-helper cell type 1 (Th1) polarisation in sarcoidosis provides the clinician with a reminder that Th1-promoting therapeutics, such as interferon-α, common variable immunodeficiency or immune reconstitution in HIV patients, are associated with development of sarcoidosis. Sarcoidosis may also be associated with autoimmune disease or cancer, although this is rare.

    An approach to sarcoidosis patients with possible rare manifestations must be individualised according to whether a diagnosis of sarcoidosis has already been established or not. As an initial step, an internet search may substantiate previous experience with similar manifestations. The clinician will often need to: 1) recommend additional diagnostic testing or biopsy, unless there is already biopsy-proven systemic sarcoidosis; and 2) check the rare manifestation is consistent with sarcoidosis and that the chance of an alternative diagnosis is low. In this latter situation, the clinician may recommend a trial of corticosteroid treatment to support an association with sarcoidosis. In patients without a confirmed diagnosis of sarcoidosis, a directed evaluation with biopsy is usually indicated.

    In all situations, the clinician must remain vigilant that unusual manifestations of sarcoidosis may, in fact, represent an alternative condition. Although the diagnostic approach to rare manifestations must be individualised, the patient and clinician are usually rewarded by establishing a link to sarcoidosis so that treatment specific to sarcoidosis can be tailored for maximal benefit.

  18. Page 251
    Correspondence: A. Clement, Paediatric Pulmonology Dept and Research Unit, INSERM U719, Hôpital d’Enfants Armand Trousseau, 26 Avenue du Dr Arnold Netter, 75571 Paris Cedex 12, France. Fax: 33 144736718; E-mail:

    Sarcoidosis is a chronic inflammatory disease in which granulomatous lesions can develop in many organs. It is a rare disease in children, affecting mainly adolescents. Its diagnosis is based on a combination of suggestive clinical features, with histologically documented noncaseating granuloma, in the absence of other known causes of granuloma formation. Information on genetic predisposition are lacking in children. The clinical expression of the disease is dominated by the involvement of the lung, eyes, skin, lymph nodes and liver. Management of paediatric patients remains empirical, due to the absence of validated criteria of disease activity and severity. Most children with sarcoidosis receive corticosteroids, a reasonable treatment duration being 18 months. The prognosis is clinically good, but long-term persistence of lung function abnormalities and alveolitis on bronchoalveolar lavage is frequently observed.

  19. Page 259
    Correspondence: U. Costabel, Dept of Pneumology/Allergy, Tüschener Weg 40, Ruhrlandklinik, D-45239 Essen, Germany. Fax: 49 2014334029; E-mail:

    The diagnostic approach to sarcoidosis is a complex procedure. There is no single diagnostic test for this disease. The diagnosis is based on three criteria: a compatible clinical and/or radiological picture, histological evidence of noncaseating granulomas, and exclusion of other diseases that may produce a similar histological or clinical picture. The diagnostic procedures should accomplish the following goals: 1) provide histological confirmation of the disease; 2) evaluate the extent and severity of organ involvement; 3) assess whether the disease is stable or likely to progress; and 4) determine if the patient will benefit from treatment.

    The clinical picture depends on the type of onset. Acute sarcoidosis has an abrupt onset and may present as Löfgren’s syndrome. Chronic sarcoidosis has an insidious onset, and organ-related symptoms are often caused by the pulmonary infiltration. It is important to know that nonspecific constitutional symptoms, including fever, weightloss, and fatigue, may occur in a high proportion of patients.

    The chest radiographic findings have various diagnostic reliability: stage I disease has an accuracy of 98% and, thus, a high diagnostic reliability, stage II is still good (89%), but the diagnostic reliability is low in the other stages. Biopsies can be obtained from easily accessable organs, such as peripheral lymph nodes, or the skin. In most cases, fibreoptic bronchoscopy with various biopsy techniques is the recommended procedure of choice. In the bronchoalveolar lavage fluid, a lymphocytosis is quite sensitive, but less specific, whereas an increased CD4+/CD8+ ratio increase is less sensitive, but highly specific for sarcoidosis. Additional tests include pulmonary function testing, laboratory tests and screening for important extrathoracic organ involvement.

    The best way to assess the activity remains through traditional clinical investigations, on the basis of onset, worsening or persistance of symptoms or signs directly related to sarcoidosis. No single biochemical or cell biological marker has a better predictive value for prognosis or disease state than the classic chest radiographic staging system.

  20. Page 265
    Correspondence: J. Verschakelen, Dept of Radiology, University Hospitals, Herestraat 49, B-3000 Leuven, Belgium. Fax: 32 16343765; E-mail:

    The diagnosis of sarcoidosis is usually established on the basis of clinical and radiological findings supported by histological findings. More than 80% of patients with sarcoidosis have intrathoracic adenopathy at the time of presentation. When hilar adenopathy is present, this intrathoracic adenopathy is often easily recognised on a chest radiograph. Computed tomography (CT) can depict additional mediastinal lymph nodes that are hardly or not visible on a chest radiograph. However, CT, and especially high-resolution CT, is especially helpful when pulmonary parenchymal disease is present. While some CT signs are moderately characteristic for the disease, CT can also play a role in the study of disease extent and can, to a certain degree, predict the reversibility of lung changes. Although magnetic resonance imaging may be useful in the evaluation of mediastinal and pulmonary involvement, the main development of this technique has taken place in the evaluation of neurosarcoidosis, and to a lesser degree in bone, muscle and cardiac sarcoidosis.

  21. Page 284
    Correspondence: J. Mañá, Servicio de Medicina Interna, Hospital Universitario de Bellvitge, Feixa Llarga s/n, L’Hospitalet de Llobregat, 08907 Barcelona, Spain. Fax: 34 932607967; E-mail:

    Nuclear imaging techniques play a role in the assessment of sarcoidosis. Several possibilities are available, and promising new techniques are in development. Scintigraphic techniques are useful in distinguishing fibrotic from active lung disease, confirming relapse in doubtful cases, assessing activity before lung transplantation and the detection of cardiac involvement and extrathoracic localisation.

    The improvement in image resolution in modern postitron emission tomography and single-photon emission computed tomography scanners, with or without computed tomography, allows more accurate imaging and quantification, whereas the use of new radiopharmaceuticals could provide more insight into the physiology and extent of the disease. In this chapter, a flow chart has been created in order to facilitate clinicians’ decisions about which tests are best to use in the assessment of sarcoidosis.

  22. Page 301
    Correspondence: R.P. Baughman, 1001 Holmes Eden Ave, Cincinnati, OH 45267-0565, USA. Fax: 1 5135585110; E-mail:

    The decision to treat a patient is dependent on many factors, the most important being whether or not the patient is symptomatic. Initial systemic therapy for symptomatic sarcoidosis usually includes corticosteroids. However, most symptomatic patients require months to years of therapy. Therefore, alternatives to corticosteroids have been studied. These include methotrexate and azathioprine. Of these two cytotoxic drugs, methotrexate has been the more extensively investigated. Both drugs work in the majority of, but not all, patients.

    Refractory sarcoidosis patients exist, who show persistent disease despite high doses of corticosteroids. Agents that block tumour necrosis factor (TNF) have been shown to be of benefit in some of these refractory cases. Thalidomide has been useful in refractory skin lesions. Infliximab, a monoclonal antibody directed against TNF has been shown to be helpful in some cases of severe refractory disease. With this array of available agents, the clinician can choose to use either single agents or combinations of agents for treating the individual sarcoidosis patient. The goal of therapy is to minimise symptoms with the lowest risk to the patient.

  23. Page 316
    Correspondence: R. Gosselink, Universitair Ziekenhuis Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Fax: 32 16347126; E-mail:

    Daily complaints of dyspnoea and fatigue, respiratory and skeletal muscle weakness, exercise intolerance, and reduced health status and quality of life have been reported in patients with sarcoidosis, irrespective of the impaired pulmonary function. Physical inactivity may be one of the underlying causes.

    Patients with sarcoidosis may benefit from an intensive exercise training programme, which has shown to improve health status, exercise capacity, skeletal muscle function and complaints of fatigue and dyspnoea in patients with other chronic diseases. Moreover, some patients with sarcoidosis may also benefit from additional therapeutic options, such as psychosocial counselling, dietary interventions and supplemental oxygen.

    Preliminary results of a randomised controlled trial studying the effects of exercise training on exercise capacity and disease-specific quality of life in patients with sarcoidosis are promising. Nonetheless, this topic merits further investigations.

  24. Page 327
    Correspondence: J.J. Egan, The Mater Misericordiae Hospital, University College Dublin, Eccles Street, Dublin 7, Ireland. Fax: 35 316605451; E-mail:

    Organ transplantation is an accepted method of treatment for sarcoidosis patients with advanced organ failure, including lung, liver or heart disease. Transplantation can be performed successfully in sarcoidosis patients. However, predicting the precise time for referral can be difficult and, therefore, early referral is advised. The management of sarcoidosis-associated pulmonary hypertension is important in this circumstance.

    Survival statistics vary but a primary diagnosis of sarcoidosis, carries an increased risk of mortality following transplantation. Recurrence is frequent (estimated to be ∼50% following lung transplantation), but is most often asymptomatic, and tends not to compromise graft function or patient survival. Regrettably, transplantation is limited by the availability of donated organs.

  25. Page 335
  26. Page 337