small-fiber neuropathy. Epidermal nerve fiber biopsy (EFNB), which is used to demonstrate loss of small unmyelinated nerve fibers, is an elegant technique available in only a few centers and can be useful to confirm an impression of small-fiber neuropathy.

9.7Management of Pain and Fatigue

Diagnosis and optimal management of SS frequently requires a multidisciplinary approach including objective evaluation of sicca complaints to document the severity and response to topical management. Investigation of neuropathic complaints to detect subtle forms of neuropathy, and evaluation for sleep disorders and depression can be important in the management of chronic fatigue and pain. Pharmacologic therapy of pain, sleep disorder, and affective disorders should be carefully tailored to minimize anticholinergic effects of medications which have the potential to increase sicca complications. Reduction of pain is optimized when all pain sources are addressed. Both central and peripheral pain mechanisms often coexist in patients with primary SS and subclinical neuropathy may be common. Gabapentin and tricyclics are effective for small-fiber neuropathy in diabetics and may have efficacy in primary SS.

The pharmacologic treatment of FM is particularly difficult. NSAIDs and opioids are not effective for central pain [121]. A trial of tricyclics, serotonin–norepineph- rine reuptake inhibitors, and/or alpha-2 delta ligands may be modestly helpful in a minority of patients, although promising results obtained in pilot studies of FM have not been duplicated thus far with only about 30% pain reduction in one half of the patients [122]. Fatigue has not been a primary outcome in most primary SS clinical trials; however, recently published randomized controlled trials of rituximab have shown a significant benefit in systemic manifestations such as cryoglobulinemic vasculitis, renal and pulmonary involvement as well as improvement in fatigue [12, 123, 124].

Psychological evaluation as part of the assessment of patients with fatigue and widespread pain is appropriate. Behavioral and psychological variables such as helplessness and poor coping predispose patients with chronic illness to increased pain and fatigue and increase the risk of affective disorder. Educational intervention targeting cognitive appraisal of illness to improve coping abilities is helpful in SLE [125]. The contribution of psychological factors to fatigue was underlined by a clinical trial of DHEA in primary SS which showed that subjects in the placebo arm experienced improvement equal to the effect on subjects in the treatment arm, demonstrating that the expectation of benefit was sufficient to improve fatigue [13]. Nonpharmacologic therapy which may be beneficial includes recommendations regarding exercise and stress management in some patients. Low-impact aerobic exercise gradually increasing in intensity, duration, and frequency may be an effective strategy in reducing fatigue in autoimmune conditions including primary SS [122, 126].

9.8Summary

Primary SS is a common systemic autoimmune disorder in which diagnosis is frequently delayed. Extraglandular manifestations of primary SS include persistent abnormal fatigue which is present in 70% and can be the presenting symptom. A cluster of symptoms: fatigue, pain, and emotional distress are often the principle reason that patients seek care. Nonspecific constitutional symptoms accompany the sicca manifestations in the majority of primary SS patients and are the predominant predictors of poor quality of life. The clinical presentation may overlap substantially with that of FM. Evaluation of and treatment for neuropathic and nociceptive sources of pain, emotional distress, and sleep quality are required for the optimal management of fatigue and improvement in the overall health status of patients with primary SS.

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Chapter 10

Musculoskeletal Involvement

Guillermo J. Pons-Estel, Bernardo A. Pons-Estel, and Graciela S. Alarcón

G.J. Pons-Estel (*)

Department of Autoimmune Diseases,

Institut Clínic de Medicina i Dermatologia, Hospital Clínic,

Barcelona, Catalonia, Spain

Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham,

Birmingham, AL, USA

e-mail: gponsestel@hotmail.com

B.A. Pons-Estel

Department of Rheumatology, Instituto Cardiovascular de Rosario, Rosario, Argentina

e-mail: baponsestel@buenaventuraguarani.com.ar

G.S. Alarcón

Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham,

Birmingham, AL, USA e-mail: galarcon@uab.edu