Patient-Reported Outcomes Including Fatigue in Primary Sjögren's Syndrome

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The hallmark of Sjögren's syndrome is focal lymphocytic infiltration of exocrine glands leading to mucosal dryness, particularly of the eyes and mouth. In addition, approximately 70% of patients report fatigue as a particularly prominent and disabling feature associated with reduced health-related quality of life. Other key patient-reported extraglandular symptoms include arthralgia, myalgia, and Raynaud's phenomenon. This article reviews these patient-reported features, their relationships with objective assessment of the disease, potential therapies for these symptoms, and how measurements of these symptoms are relevant to outcome assessment in clinical therapeutic trials.

Section snippets

Fatigue

Fatigue is also commonly reported by patients with other rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus.2, 3, 4 Furthermore, fatigue is relatively common in the general population9 and can present in association with certain medical conditions (eg, hypothyroidism), or with psychiatric diseases (eg depression), or be medically unexplained (eg, chronic fatigue syndrome).9 One useful model, therefore, considers the interrelationships of biological (eg, “disease

Measurement of fatigue and other extraglandular symptoms

The simplest way of measuring fatigue (or indeed other symptoms, such as joint/muscle pain or Raynaud's) is to use a 10-cm visual analog scale (VAS) asking the patient to rate his or her fatigue (ie, from “none” at minimum to “worst fatigue imaginable” at most). Another approach is to use a questionnaire comprising a series of questions, each of which addresses some different component of the symptom under evaluation (Table 1). Some of these fatigue questionnaires eg, the Functional Assessment

Potential approaches to treatment of fatigue and other extraglandular symptoms

The most commonly used medication in our experience to treat fatigue and joint/muscle pain in PSS is hydroxychloroquine. Fox and colleagues30 reported improvement in arthralgia and myalgia (five-point Likert scale) in an open-label retrospective study in 50 patients treated for a minimum of 2 years with hydroxychloroquine 6 to 7 mg/kg/d. Kruize and colleagues31 in 2003 performed a small crossover study in 19 patients over 2 years (12 months on placebo or hydroxychloroquine 400 mg/d switched to

Dryness (sicca) symptoms

Dryness is the key symptom of Sjögren's syndrome, with oral and ocular dryness as the most common and troublesome component.1 As with fatigue, pain, or other extraglandular symptoms, the simplest way to measure dryness is with a VAS, but questionnaires can add detail and reliability. A number of dryness questionnaires have been developed. Many are screening questionnaires to identify the presence or absence of dryness symptoms in the community or as part of classification criteria for Sjögren's

Data from existing clinical studies

The largest trial of therapy of oral and ocular dryness in Sjögren's syndrome was performed by Vivino and colleagues50 in 1999. They studied 373 patients with primary or secondary Sjögren's syndrome randomized to placebo (n = 125) or 2.5 mg pilocarpine four times a day (n = 121) or 5 mg pilocarpine four times a day (n = 127) for 12 weeks. Pilocarpine is a muscarinic agonist that stimulates exocrine glands. Five milligrams of pilocarpine was effective in stimulating salivary flow at the start

Summary: measurement of patient-reported outcomes in clinical trials

The work described here has identified dryness and fatigue as the key patient-reported outcomes in PSS (with joint pain and Raynaud's also being frequent). In expert panel discussions, fatigue was felt to be a particularly important outcome domain in its own right, in relation to patients' disease experience.60, 61 We have also shown that fatigue can improve following systemic therapy20 and there is increasing interest in fatigue as a secondary outcome measure in rheumatoid arthritis.25, 40

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