Epidemiology

Sjögren syndrome is a slowly progressive dysfunction of the lacrimal and salivary glands. The resulting exocrinopathy produces the characteristic symptoms of dry eyes and dry mouth. An incidence of 4 per 100,000 per year has been noted. Ninety percent of cases occur in women, and the incidence increases with age. Patients may be anywhere in age from the fourth to the eighth decades.

Pathophysiology

Activation of the innate immune system, possibly in response to environmental or as yet unrecognized infectious triggers, results in elevated levels of type 1 interferon and characteristic cytokine profiles, including increased B-cell–activating factor. The ensuing infiltration of the salivary or lacrimal glands by periductal and periacinar foci of aggressive T lymphocytes marks the adaptive immune response. What follows is destruction and eventual loss of exocrine function.¹ In addition to T cells, polyclonal activation of B cells within and at the border of foci can result in hypergammaglobulinemia.

More recently, animal models suggest that lacrimal and salivary gland dysfunction need not always rely on innate and adaptive inflammation as a prerequisite. Rather, they may be related to abnormalities in water and ion channels as a result of genetic, hormonal, or autonomic imbalances antecedent to the inflammatory response.² Other exocrine glands in the body (lining the respiratory tree, integument, and vagina) can also be affected in Sjögren syndrome and produce a dry cough, dry skin, dysuria, or dyspareunia.

Regardless of whether the lacrimal and salivary gland dysfunction is bound to an inflammatory infiltrate, it is known that the hallmark of Sjögren syndrome is eventual systemic lymphocyte activation, which means that organs other than glandular tissue can be affected. Such a level of immune activation could be responsible for the increased risk for lymphoproliferative disorders and autoimmune endocrinopathies that have been noted in patients with Sjögren syndrome.

Presenting Signs and Symptoms

Differential Diagnosis and Medical Decision Making

If dry eyes and dry mouth dominate the clinical picture, the patient may have primary Sjögren syndrome. However, these symptoms can be associated with a number of other autoimmune disorders that more accurately characterize the clinical findings (rheumatoid arthritis, systemic lupus erythematosus, scleroderma), in which case such patients probably have secondary Sjögren syndrome (Box 109.1).

The cracker test, in which the patient tries to chew and swallow a dry cracker, is probably the most useful bedside diagnostic maneuver. Patients with Sjögren syndrome will have a difficult time completing this task, with adherence of food to the buccal mucosa. Slit-lamp testing with fluorescein may show epithelial defects over the cornea consistent with keratitis secondary to dryness. Rose bengal staining (Fig. 109.1) is generally regarded as a more sensitive means of depicting these defects but is usually performed by an ophthalmologist. The Schirmer test involves placing standardized tear testing strips between the unanesthetized eyeball and the lateral margin of the lower lid and noting advancement of a tear film over a period of 5 minutes. Anything less than 5 mm is considered abnormal.

Fig. 109.1 Keratitis seen with rose bengal stain.

(From Yanoff M, Duker JS, editors. Ophthalmology. 2nd ed. St. Louis: Mosby; 2004.)

Treatment

Treatment of Sjögren syndrome has two objectives: improve the symptoms of exocrine gland dysfunction and attempt to control the underlying autoimmune lymphocyte activity. The former has had more success than the latter.

Patient Disposition and Next Steps in Care

Patients with suspected primary or secondary Sjögren syndrome should undergo outpatient primary care and rheumatology follow-up within 2 to 4 weeks. Outpatient ophthalmology or dental evaluation is also advisable. Patients should be told to return to the ED for significant ocular pain or visual disturbance, which may signify keratitis and can be complicated by globe perforation.

Epidemiology

Systemic sclerosis is a generalized thickening and fibrosis of the skin and internal organs that affects 1 in 4000 adults in the United States.¹⁰ Its incidence ranges from 2 to 23 cases per million per year.¹¹ Women are more likely to be affected than men, with the onset of disease peaking between 30 and 50 years of age.

Pathophysiology

Patients can have localized patches of skin fibrosis, or the disorder may progress to diffuse skin involvement with fibrosis and dysfunction of internal organs. Although the precise trigger is not known, an underlying functional and microstructural vascular abnormality is believed to play a central role. In association with oxygen radical species, findings include endothelial cell dysfunction and apoptosis, an imbalance favoring endothelin over prostacyclin, vascular smooth muscle hyperplasia, and pericyte proliferation in the perivascular space. Concomitantly, an adjacent inflammatory response occurs and is composed of lymphocytes, macrophages, and fibroblasts that lay down increasing amounts of extracellular matrix, including collagen.¹² Cytokines and growth factors such as transforming growth factor-β and platelet-derived growth factor are involved in the amplification of this response, which includes activation and differentiation of fibroblasts.¹⁰ The types of systemic sclerosis are listed in Box 109.2.

Presenting Signs and Symptoms

Raynaud phenomenon is the initial complaint in the majority of patients and precedes clinically detectable skin fibrosis, probably because vascular malfunction antedates the edema and collagen deposition in patients with systemic sclerosis. The skin blanching associated with Raynaud phenomenon may not be present, but paresthesias or sensory deficits followed by throbbing pain in the fingers, toes, and sometimes the cheeks, nose, or tongue on exposure to cold are more consistent findings. It should be noted, however, that systemic sclerosis never develops in most patients with Raynaud phenomenon.

Musculoskeletal complaints consisting of arthralgias, myalgias, and generalized weakness are nearly universal in patients with systemic sclerosis and other connective tissue disorders. Sometimes patients will have palpable or audible tendon friction rubs. Musculoskeletal problems are often some of the first symptoms and may be refractory to standard therapy with NSAIDs.

Skin findings are the most useful in the ED. Edema is a hallmark of early scleroderma, as well as rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Painless swelling of the fingers and hands is common (Fig. 109.2). Erythema and pruritus are associated findings caused by an early inflammatory response and deposition of components of the extracellular matrix. Nonpitting edema need not be limited to the distal end of extremities but may spread proximally or to the face and neck over the course of weeks.

Fig. 109.2 Changes in the hands associated with connective tissue diseases.

A, Edematous phase. B, Atrophic phase with contractures and skin thickening (sclerodactyly).

(From Goldman L, Ausiello D, editors. Cecil textbook of medicine. 22nd ed. Philadelphia: Saunders; 2004.)

Fibrosis can ensue in weeks or months. Gradually, collagen is deposited and the edematous areas are replaced by firm, thick, taut skin that may become bound to underlying tissue. In the fingers, tight skin can produce joint flexion contractures plus breaks or ulcerations as it is stretched over bony prominences (knuckles) in the condition termed sclerodactyly (see Fig. 109.2