«Sarcoidosis: joint, muscle and bone involvement T.L.Th.A. Jansen*, P.P.M.M. Geusens# *Medical Centre Leeuwarden, Dept of Rheumatology, Leeuwarden, ...»
Sarcoidosis: joint, muscle and bone
T.L.Th.A. Jansen*, P.P.M.M. Geusens#
*Medical Centre Leeuwarden, Dept of Rheumatology, Leeuwarden, and #University Hospital Maastricht,
Dept of Rheumatology, Sarcoidosis Management Center, Maastricht, The Netherlands and Biomedical
Research Institute, University Hasselt, Belgium.
Correspondence: T.L.Th.A. Jansen, Medical Centre Leeuwarden, Dept of Rheumatology, POB 888, 8901
BR Leeuwarden, The Netherlands. E-mail: firstname.lastname@example.org Sarcoidosis is a multisystem granulomotous disease in which multiple organs, including the locomotor system, may be involved [1–5]. Osteoarticular manifestations of sarcoidosis may be speciﬁc or nonspeciﬁc. They may be the presenting feature or may occur late after onset, either isolated or combined with other clinical manifestations.
Clinical features of joint involvement are found in 14% of cases at presentation, and up to 38% during follow-up . The frequency of clinical muscle and bone involvement at presentation is low (v1%), and is found in 5–13% of patients during follow-up .
Locomotor involvement is often subclinical or not clinically recognised because of mild or unspeciﬁc symptoms in spite of a high prevalence on biopsy, as shown for muscle involvement . Another systemic locomotor sequel is secondary osteoporosis, mostly due to glucocorticoid therapy .
Sarcoid joint involvement Joint manifestations, including arthritis and periarthritis, occur in 14–38% of patients [1–5]. Arthralgias are even more common (70%) . Sarcoid rheumatic involvement is generally divided into acute and chronic types [1–5]. There are so many differences between acute and chronic arthritis that is has been questioned whether they represent the same aspects of sarcoid joint disease .
Acute sarcoid arthritis The most common form of joint involvement is an acute polyarthritis/periarthritis.
The arthritis may be migratory, intermittent or additive in time, and can precede other manifestations of sarcoidosis by several months. These clinical presentations can, therefore, resemble reactive arthritis , rheumatoid arthritis or even spondylarthropathies . More commonly, however, it is nonmigratory and accompanied by other signs of sarcoidosis , known as the Lofgren’s syndrome [7–9].
¨ Classically, Lofgren’s syndrome consists of a triad with bilateral hilar lymphadeno¨ pathy, erythema nodosum and (peri)arthritis of large joints, particularly of the ankles and knees, although other peripheral large and small joints can be involved [7–9]. This presentation of acute sarcoidosis most frequently occurs in Caucasian females and is rare in Afro-Americans . Fever and other constitutional symptoms commonly accompany Eur Respir Mon, 2005, 32, 210–219. Printed in UK - all rights reserved. Copyright ERS Journals Ltd 2005; European Respiratory Monograph;
ISSN 1025-448x. ISBN 1-904097-22-7.
RHEUMATIC PRESENTATIONS IN SARCOIDOSISacute sarcoid arthritis. Seasonal variation of acute sarcoid arthritis has been reported with clustering in the spring [7, 9].
In a series of 186 Spanish patients with Lofgren’s syndrome, 93% had erythema ¨ nodosum and/or periarticular ankle inﬂammation at onset [9, 10]. At the time of diagnosis 81% had no respiratory symptoms. In contrast, 81% had stage I abnormalities on chest radiography, 16% stage II and 3% stage 0. Sonographic ﬁndings in 24 consecutive cases revealed joint effusion consistent with arthritis in 33%, periarthritis in 80% and a tenosynovitis in 33% patients .
Prognostically, Lofgren’s syndrome is not recurrent in the majority of cases. In 17 ¨ cases followed prospectively over 2 yrs, the total duration of arthritis was 11 weeks (range 2–107 weeks) and erythema nodosum was mild and transient . Of the 133 patients who were followed for a mean of almost 5 yrs, 8% continued to have active disease and 6% had several recurrences between 18 months and 20 yrs after complete resolution, although usually with mild organ dysfunction . Thus, acute sarcoidosis classiﬁed as Lofgren’s syndrome has a favourable prognosis, except in Afro-Americans ¨ and Asians . Prolonged monitoring is necessary where prognosis is not so good.
Clinical features of acute or subacute monoarthritis, other than Lofgren’s syndrome, ¨ are only rarely reported . Synovial ﬂuid is inﬂammatory, with predominance of lymphocytes . Synovial or soft tissue biopsies can reveal granulomatous lesions .
There may be protracted courses and recurrences of arthritis .
Chronic sarcoid arthritis Chronic sarcoid articular involvement is rare and appears to affect only 0.2% of sarcoid patients [12, 13], usually together with other complications of sarcoidosis, particularly chronic cutaneous sarcoidosis  and in Black patients [2, 3]. Medium-sized and large joints are often affected symmetrically and a simulataneous tenosynovitis may occur. Some cases have been described with severe destructive arthropathy requiring total arthroplasty . Synovial biopsy shows noncaseating granulomas. In some cases, rheumatoid arthritis may be suspected, particularly when there is a coincident rheumatoid factor, occurring in y30%. The course of chronic sarcoid arthritis is characterised by periodic exacerbation and improvement with a good functional outcome . However, joint destruction or deformities may be seen, including Jaccoud’s type arthropathy .
In children, a chronic juvenile arthritis may be mimicked by combination of polyarthritis, uveitis and skin lesions . A positive synovial biopsy may help establish the diagnosis.
Sarcoid synovial and tendinous involvement Periarticular manifestations appear much more commonly than previously thought, in some reports in w60% of patients [2, 16, 17]. Tenosynovitis, articular cysts or inﬁltration of subcutaneous tissue causing elephant foot-like thickening have been reported .
Tenosynovitis usually affects extensor tendons of the ﬁngers more often than ﬂexor tendons, but carpal tunnel syndrome may also manifest itself . Biopsy of synovium, tendon sheaths or subcutaneous tissue may reveal noncaseating granulomas.
Some bone locations, such as dactylitis and sacroiliac location, are associated with clinical and/or radiographic signs of joint involvement. These are further described in the section on sarcoid bone involvement (see later).
T.L.TH.A. JANSEN AND P.P.M.M. GEUSENS Treatment of sarcoid joint involvement In cases of acute sarcoid arthritis, most frequently it is sufﬁcient to give cold packs t.i.d. with a training programme combined with nonsteroidal anti-inﬂammatory drugs (NSAIDs) (table 1) . The outcome of articular involvement is generally favourable as recovery is uneventful, generally within 1–6 months . According to open label studies, sarcoid arthritis has also been treated efﬁcaciously by systemic glucocorticoids and colchicine (oral or i.v.) . Periarthritis is often responsive to rest, cold application and NSAIDs, whereas glucocorticoids are generally not needed nor recommended.
A chronic destructive synovitis may need treatment with glucocorticoids intraarticularly or systemically, and, in the latter case, is probably best combined with methotrexate or azathioprine, though ﬁrm evidence from randomised controlled trials is lacking [1–5]. Possibly, there is an indication for an anti-tumour necrosis factor (TNF)-a strategy in selective cases with chronic destructive arthritis in the near future.
In children, a much more aggressive treatment is needed, often comprising of a combination of glucocorticoids with immunosuppressants .
Sarcoid muscular involvement There are several reasons why some patients with sarcoidosis develop muscle problems, including involvement of the skeletal muscle by sarcoidosis, steroid-induced myopathy, small ﬁbre neuropathy and reduced physical activity.
Sarcoid muscle involvement is usually asymptomatic and resolves spontaneously, although granulomas are commonly demonstrated by biopsy in 50–80% of sarcoid cases . In a group of 29 sarcoid patients who spontaneously complained of fatigue, skeletal muscle weakness was found that was associated with reduced health status and exercise intolerance . Gallium scintigraphy is considered the main method that can demonstrate muscular involvement . In some cases magnetic resonance imaging (MRI) can be helpful for diagnosis, but small lesions can be overlooked .
Rarely, acute inﬂammatory myopathy resembling polymyositis, as well as palpable myopathic nodules and a chronic progressive myopathy, have been described [6, 20–23].
The latter myopathic type occurs predominantly in elderly females with a painful bilateral involvement and often results in muscle weakness, atrophy and even muscle contracture .
The rarest type is the acute sarcoid myositis, as is reported in 18 cases [20, 22]. This is usually found in younger patients with proximal muscle weakness mimicking acute polymyositis.
The diaphragm and intercostal muscles may also be impaired. It has been demonstrated that patients with sarcoid granulomas inﬁltrating skeletal muscle had Table 1. – Treatment options in sarcoidosis with locomotor complaints
impaired respiratory muscle function [18, 24]. With a lack of a correlation between subjective symptoms, i.e. exertional dyspnoea and/or fatigue, and chest radiograph abnormalities, lung function may be explained by respiratory muscle impairment. The relevance of inspiratory muscle impairment in sarcoid patients is underscored by signiﬁcant correlations found between dyspnoea scores and health status and quality of life [25–27]. In addition, it has been shown that small ﬁbre neuropathy is a frequent ﬁnding of sarcoid patients with fatigue .
Treatment of sarcoid muscle involvement There are currently no studies available on the treatment of sarcoid muscle involvement. In severe cases, glucocorticoids and immunosuppressive drugs are given (table 1). For patients with muscle weakness, controlled physical training programmes are advocated, as shown in other conditions [17, 29].
Sarcoid bone involvement In 1928, Jungling described osteitis tuberculosa multiplex cystica with an estimated incidence of 1–13%, the variation depending on radiological or clinical criteria . Bone involvement occurs between the ages of 30–50 yrs and is more frequent in Blacks. It is rarely a presenting feature (in v1% of patients)  and usually occurs in patients known to have sarcoidosis with multisystemic involvement, in chronic pulmonary or multivisceral sarcoidosis and in patients with chronic skin lesions, especially lupus pernio . Bone lesions are mainly seen in the bones of hands and feet, but other locations, such as the skull, nasal bones and vertebrae, have been described. They are usually asymptomatic, but may be painful, and, in case of severe lesions, adjacent joints can be involved . Radiological ﬁndings most frequently show cystic lesions, punchedout lesions, osteolysis, reticularisation of cortical bone or cortical defects and, rarely, sclerotic, periostitis or destructive lesions [4, 31–33].
Biopsy reveals granulomas in the medullary cavity and destruction of the adjacent bone tissue [31–33]. Thereby conﬂuent lacunae and cavities of varying sizes surrounded by normal bone may occur. Margins may reveal subsequent sclerosis. Granulomatous tissue may affect the periosteum and may invade neightbouring soft tissue.
Histomorphometry has shown increased bone resorption in the vicinity of intramedullary sarcoid nodules, probably due to local mediators .
On technetium bone scanning an increased uptake is seen, suggesting, or sometimes mimicking, neoplastic lesions . To differentiate these from sarcoid lesions additional imaging may be needed. Computed tomography (CT) scanning shows bone destruction or sclerosis, particularly marginally, without extra-osseous mass or extension to soft tissues. MRI scanning shows nonspeciﬁc lesions with a reduced signal on T1, and increased signal on T2-weighted sequences, enhanced by Gadolinium. The combination of these features does not preclude a neoplastic or infectious condition . There is no indication for routine radioisotope bone scanning in patients with sarcoidosis, and this examination should be restricted to patients with clinical suspicion of osseous sarcoidosis .
Dactylitis Involvement of ﬁngers, particularly 2nd and 3rd digits, and less frequently of toes, is the most frequent bone manifestation . Dactylitis may be asymptomatic but may also T.L.TH.A. JANSEN AND P.P.M.M. GEUSENS cause moderate pain and stiffness. Distal phalangeal swellings are associated with purpleviolet, cyanotic discolouration, and splitting of nails or nail dystrophy. Acro-osteolysis may give the appearance of pseudo-clubbing or sausage-like ﬁngers .
Pelvic pathology Involvement of the pelvis is featured by bony sclerosis, sometimes with lytic lesions and surrounding condensation. In the majority of patients it is symptomatic, i.e. painful . A genuine sacroiliitis is rare, and in the literature this is reported only once .
Sacroiliac pathology is considered to be secondary to conﬂuencing bone lesions of sacrum and ilium. Such localisation cannot be established without a biopsy to rule out tuberculosis or other infectious processes of that joint .
Skull Lesions of the vault of the skull are rare. Less than 30 cases have been reported .
The incidence may be underestimated, as symptoms generally are absent or only minor, such as headache or local swelling. Bony lacunae vary in size and localisation.
Radiographs show osteolysis of full thickness of the skull without peri-lesional condensation. Cases of partial or complete regression, both spontaneous or with treatment, have been described. Involvement of the base and of other cranial bones, i.e.
sinus, petrous bones, orbits, mandible, and nasal bone, seems to be found more frequently with the widespread use of facial CT scans .