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). Digital ulcerations, pitting scars, and loss of the finger pad can result from poor distal perfusion through intervening fibrotic tissue. This may be followed by calcium deposition (calcinosis).

A masklike appearance of the face (Fig. 109.3) with loss of the natural skin creases and diminished hair growth is characteristic. “Salt and pepper” alterations in pigmentation may be present. Disorganized arrays of blood vessels (telangiectases) scattered over the extremities, face, and mucous membranes are sequelae of deranged angiogenesis after the initial vascular obliteration and fibrotic inflammatory response.

Fig. 109.3 Facial features in scleroderma.

Note the vertical lines or furrowing around the mouth in this patient with diffuse scleroderma.

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

Gastrointestinal symptoms are very common and related to intestinal wall edema and fibrosis, which can occur anywhere from the esophagus to the rectum. Reflux esophagitis, strictures, and even Barrett esophagus can occur. Throughout the rest of the bowel, complications include smooth muscle dysfunction with dysmotility and ileus, pulsion diverticula as a result of uncoordinated peristaltic activity, bacterial overgrowth, and malabsorption. Nausea, anorexia, bloating, constipation, and diarrhea are potential complaints.

Pulmonary symptoms generally include dyspnea on exertion and a nonproductive cough. Interstitial fibrosis is more common in the diffuse form of scleroderma, and scattered rales may be heard. As with other fibrotic conditions, systemic sclerosis produces a restrictive lung disease. Pulmonary hypertension from obliteration of pulmonary vasculature associated with changes in the intimal and medial vessel walls can occur in the absence of significant interstitial fibrosis and is seen in a subset of patients with the limited form of systemic sclerosis.

Renal vascular involvement parallels that of other organs. The main difference is that when flow through the arcuate and interlobular renal arterioles is diminished secondary to the microvasculopathy and spasm characteristic of systemic sclerosis, the distal glomerulus and juxtaglomerular apparatus will respond to this decrease in perfusion by producing renin and beginning a cycle of fluid retention and vascular constriction via angiotensin II and aldosterone. The result is hypertension with systemic vasoconstriction, which can cause further damage to blood vessels and even hemolysis of red cells as they pass through the injured vasculature. In this sense, patients with renal involvement can seen be anywhere along a spectrum between asymptomatic hypertension and a hypertensive emergency or malignant hypertension with characteristic funduscopic changes.

Cardiac inflammation results in pericarditis with effusion. In the myocardium, patchy areas of fibrosis can physically impair cardiac conduction or provide scar tissue that serves as points of electrical reentry. Secondary conduction deficits and supraventricular or ventricular arrhythmias will follow. Myocardial involvement and arrhythmias are asymptomatic in most, but dyspnea on exertion, congestive heart failure, syncope, or sudden death can occur. Additionally, coronary artery vasospasm may be associated with the underlying vasculopathy of systemic sclerosis.

Other features include thyroid, salivary, and lacrimal gland dysfunction secondary to fibrosis. Fibrosis in soft tissue can result in an entrapment neuropathy of susceptible peripheral nerves, including the median, lateral femoral cutaneous, trigeminal, and facial nerves. Men may have erectile dysfunction from impaired blood flow secondary to vasculopathy and fibrosis.

Differential Diagnosis and Medical Decision Making

The differential diagnosis for systemic sclerosis includes several other connective tissue diseases (Box 109.3).

Skin examination is the most important diagnostic tool for the emergency physician (EP). Nail fold capillary examination may be useful for patients with Raynaud phenomenon who do not yet have skin changes indicative of sclerosis. Using an ophthalmoscope and immersion oil applied to the skin, dilated and tortuous capillaries mixed with areas of capillary loss can be seen as evidence of a burgeoning connective tissue disease in patients with secondary Raynaud phenomenon.

Serum electrolyte levels should be measured and urinalysis performed to evaluate renal function. Because the disease does not usually involve the glomerulus or nephron tubular cells directly, but rather the arterioles upstream, findings on urinalysis are frequently normal or limited to mild proteinuria with few cells or casts. Therefore, elevations in serum creatinine alone in a patient with other clinical evidence of systemic sclerosis would raise the possibility of scleroderma renal disease.

A complete blood count and smear should be obtained for patients with suspected microangiopathic hemolysis from malignant hypertension. An electrocardiogram and rhythm strip can be evaluated for suspected conduction deficits or arrhythmia secondary to myocardial fibrosis.

Nonemergency work-up includes specific autoantibody profiling, gastrointestinal contrast studies for dysmotility, pulmonary function testing, echocardiography to evaluate myocardial contractile function or pulmonary hypertension, and biopsy to reveal the characteristic fibrotic skin or gland changes.

Treatment

Because the mechanics and primary inciting events of systemic sclerosis are not yet well understood, therapy is generally aimed at improving symptoms and curbing end-organ dysfunction. Treatment of Raynaud phenomenon includes lifestyle changes, calcium channel blockers, alpha-blockers, antiplatelet agents, and sympathectomy.

Musculoskeletal symptoms may respond to ibuprofen or another NSAID in standard doses combined with physical and occupational therapy.

Skin therapy includes moisturizers, topical glucocorticoid or antihistamine cream for pruritus, and local wound care with topical antibiotics for ulceration. High- or low-dose D-penicillamine cannot be recommended as an effective treatment at this time.¹³

Gastroesophageal reflux responds to standard changes in dietary habits and daily oral administration of omeprazole, 10 to 20 mg. Refractory cases may require surgical intervention, and reflux esophagitis–induced strictures may need periodic dilation.

Pulmonary hypertension is managed with endothelin receptor antagonists, phosphodiesterase inhibitors, and prostacyclin analogues.^10,14 Control of interstitial fibrosis has proved more difficult. Aggressive treatment with methotrexate, cyclophosphamide, or other immunosuppressives should be left to a specialist because their benefit is unclear.

Asymptomatic hypertension in a patient with known or suspected systemic sclerosis is presumed to be hyperreninemic in origin secondary to renal arteriolar disease and should be treated as such with an angiotensin-converting enzyme inhibitor. Oral administration of captopril, 6.25 to 12.5 mg three times per day, is a recommended starting point.^15,16 These patients require close outpatient monitoring of renal function. Patients with a hypertensive emergency or malignant hypertension may require intravenous enalaprilat or tighter control of systemic vascular resistance and heart rate via short-acting agents. Dialysis and renal transplantation remain last-line treatments for patients whose condition progresses to end-stage renal disease despite medical management.

Current emerging therapies include intravenous immune globulin, mycophenolate mofetil, B-cell antibodies (rituximab), and autologous or allogeneic hematopoietic stem cell transplantation to curb the role of immune cells in the pathogenesis of systemic sclerosis. Interferon therapy, downstream tyrosine kinase inhibition, and other novel antifibrotic approaches may be used to limit fibroblast proliferation and collagen production in the future.¹⁷

Epidemiology

Because granulomatous inflammation can be due to many causes, the exact worldwide prevalence and incidence of sarcoidosis are not known. Most patients with the disease are younger than 50 years, and the peak age seems to be 20 to 39 years. Women are affected slightly more often than men. Worldwide, the majority of cases occur in white persons in northern European countries, but in the United States the disease is more frequent in African Americans.¹⁸

Pathophysiology

Sarcoidosis is characterized by the presence of noncaseating granulomas in multiple organs. Granulomas are composed of macrophages and other antigen-presenting cells, as well as T lymphocytes helping organize the response. They represent the immunologic reaction to organisms or antigens that cannot be properly disposed of and instead are simply contained and walled off. Sometimes the contents of the granuloma undergo what is described pathologically as caseous necrosis (i.e., the granulomatous response to tuberculosis). At other times necrosis is absent, and the granulomas are termed noncaseating. In sarcoidosis, noncaseating granulomas can be found anywhere in the body but are primarily situated in the mediastinal and hilar lymphatic tissue, airways, and pulmonary parenchyma. Respiratory or not, nearly every clinical manifestation of sarcoidosis can be traced to the physical presence of granulomas within the organ.

Although the exact cause of sarcoidosis is unknown, some evidence indicates that an environmental, chemical, or infectious agent provides the antigenic stimulus to macrophages. Once processed and presented, these antigens trigger a CD4⁺ T-cell–mediated reaction that subsequently incites increasing numbers of macrophages and neighboring epithelial cells to partake in the formation of noncaseating granulomas and thereby produce the clinical signs and symptoms of sarcoidosis.

In addition to the environmental trigger, a genetic component mediating T-cell hypersensitivity may be required. In this way, clinical sarcoidosis may develop in only a genetically susceptible individual exposed to the unidentified antigen.

Presenting Signs and Symptoms

Pulmonary disease is the hallmark of sarcoidosis. Granulomas occur throughout the mediastinal and hilar lymph nodes, in the lining of bronchi, and within the pulmonary parenchyma. Dyspnea on exertion, nonproductive cough, and nonspecific retrosternal chest pain are common complaints. Depending on the location and extent of the granulomatous tissue, patients may have primarily wheezing and a prolonged expiratory phase from endobronchial lesions or rales from parenchymal involvement. Alternatively, many patients have no symptoms and clear lung findings despite radiographic evidence of disease.

Skin lesions are present in up to 25% of patients (Fig. 109.4). Most are chronic and due to direct granulomatous involvement of the dermis. Unfortunately, they may take the form of papules, plaques, nodules, keloids at the site of surgical scars, or even lupus pernio (a violaceous discoloration over the nose, cheeks, chin, and ears). Thus it is difficult for the EP to make the diagnosis of sarcoidosis based on the presence of skin lesions alone.

Fig. 109.4 Skin lesions of sarcoidosis.

A, Sarcoid lesions may occur at any site, and they may take a nodular, papular, or plaque form. Biopsy is often necessary for diagnosis. B, Lupus pernio is the term used to describe a dusky-purple infiltration of the skin of the nose, cheeks, or ears in chronic sarcoidosis.

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

Erythema nodosum may be one exception. Unlike other lesions, it is acute in onset and does not consist of granulomas but instead cellular inflammation and edema involving the dermis and subcutaneous tissue; it produces the characteristic raised, red, tender, nodular lesions most often seen on the anterior tibial surface. Erythema nodosum can be used to confirm the diagnosis of sarcoidosis in patients found to have bilateral hilar lymphadenopathy on chest radiography.

This combination of findings describes a subset of sarcoidosis patients said to have Löfgren syndrome. Note that erythema nodosum without bilateral hilar adenopathy may be present in a number of other infectious or neoplastic conditions and should not be considered diagnostic of sarcoidosis.

Ocular sarcoidosis most frequently takes the form of anterior uveitis with symptoms of eye pain, irritation, and visual disturbances, including red eye and photophobia. Cell and flare or even hypopyon may be seen on slit-lamp examination. Posterior uveal tissue can also be involved, with signs of chorioretinitis noted on funduscopy. Keratitis and globe perforation are sequelae of corneal involvement, and nodules representative of granulomatous tissue can be seen on the conjunctiva of affected patients.

Cardiac disease, though less common, can be life-threatening. Appropriately placed septal granulomas can block the normal conduction system, with complete heart block being the most common manifestation. They may also serve as foci for electrical reentry and thereby predispose to arrhythmias. Within papillary tissue, granulomas can result in muscle dysfunction and secondary atrioventricular valve incompetence. Extensive ventricular muscle involvement or valvular insufficiency can result in congestive heart failure.

Musculoskeletal manifestations consist of symmetric arthralgias or inflammatory arthritis of the ankles, knees, wrists, and elbows. Most patients do not have a chronic destructive arthritis, however. Although lytic or sclerotic bony lesions can be noted in the hands and feet, many patients will be asymptomatic. Granulomatous muscle involvement is also often subclinical.

Neurologic complications develop in up to 10% of patients and can involve any part of the central or peripheral nervous system. Aseptic (predominantly basal) meningitis, encephalopathy, seizures, hypothalamic and pituitary disturbances (with diabetes insipidus or secondary thyroid or adrenal dysfunction), cranial neuropathies (especially unilateral or bilateral cranial nerve VII palsies), and communicating or noncommunicating hydrocephalus from granulomatous impairment of ventricular drainage are all potential intracranial manifestations. Peripheral neuropathies and spinal cord dysfunction are secondary to extracranial granulomatous inflammation.

Glandular exocrine insufficiency from granulomatous involvement can produce swollen lacrimal, parotid, and salivary glands, with resultant symptoms of dry eyes and mouth. Other signs and symptoms related to systemic T-cell activation and granuloma formation include nonthoracic lymphadenopathy, splenomegaly, fever, and malaise. Increased granulomatous calcitriol production with long-standing hypercalcemia and hypercalciuria may result in renal calcium deposition.

Differential Diagnosis and Medical Decision Making

Pulmonary symptoms and typical radiographic signs in a young or middle-aged patient with erythema nodosum, iritis, or nonspecific, symmetric musculoskeletal complaints can help the EP distinguish sarcoidosis from other infectious or autoimmune processes (Table 109.1). Even then, a definitive bedside diagnosis may be difficult to make, and the EP may need to consider tuberculosis, histoplasmosis, community-acquired pneumonia, and lymphoma before diagnosing sarcoidosis (Box 109.4). Some of these patients will have to be admitted or treated empirically for an infectious process before a diagnosis can be secured via a more extensive work-up. Given the array of organ systems affected and the lack of pulmonary symptoms in many patients, sarcoidosis may go unrecognized in the ED.

A chest radiograph is the most useful tool for patients with cough, dyspnea, or chest pain. Patients in whom the diagnosis of sarcoidosis is being considered because of erythema nodosum, iritis, or cranial neuropathy should also undergo chest radiography, even in the absence of pulmonary signs or symptoms. The four stages of pulmonary sarcoidosis are described in Table 109.2. Patients normally do not progress from one stage to the next. A higher stage indicates a lower likelihood of spontaneous resolution.

Table 109.2 Stages of Pulmonary Sarcoidosis

Fig. 109.5 A, Stage I sarcoidosis: prominent hilar lymphadenopathy and normal lungs. B, Stage III sarcoidosis: interstitial infiltrate without hilar lymphadenopathy.

(From Mason RJ, Broaddus VC, Murray JF, et al. Murray and Nadel’s textbook of respiratory medicine. 4th ed. Philadelphia: Saunders; 2004.)

An electrocardiogram should be obtained for any patient with syncope, dyspnea, or rhythm abnormalities. Cardiac granulomas can produce first- through third-degree atrioventricular block, fascicular block, or bundle branch block.

Patients should undergo a slit-lamp examination for evaluation of the red eye. Consensual photophobia, pain at a given distance of accommodation, and cell and flare are indicative of iritis. Funduscopic examination may provide evidence of posterior uveitis (vitreous, retinal, or choroid disease). Corneal staining and the Seidel test are useful for the diagnosis of keratitis and corneal perforation.

Findings on arthrocentesis will be consistent with nonseptic, inflammatory arthritis. A computed tomography scan of the brain or a lumbar puncture should be performed in patients with suspected focal intracranial or diffuse meningeal neurologic involvement. Two thirds of patients will have elevated cerebrospinal fluid protein, and half may have a predominantly mononuclear pleocytosis. These findings in some patients with extraneural sarcoid features may suggest the diagnosis of neurosarcoidosis.

Laboratory work will probably not help the EP make a diagnosis, but findings may include anemia of chronic disease, thrombocytopenia from splenomegaly, elevated serum calcium levels from granuloma-related abnormalities in calcitriol production, and nonspecific transaminitis as a result of asymptomatic hepatic granulomas.

Further work-up consisting of a tuberculin skin test, chest computed tomography scan, pulmonary function tests, echocardiography, angiotensin-converting enzyme levels, radionuclide imaging, endomyocardial biopsy for myocardial involvement, bronchoalveolar lavage, or endobronchial, transbronchial, mediastinal, or thoracoscopic biopsy may be considered for patients on an inpatient or outpatient basis with specialist consultation.

Treatment

Two thirds of cases of sarcoidosis will resolve spontaneously within 2 years, and many patients can be managed by observation alone. Treatment focuses on suppression of granuloma formation with glucocorticoids and is reserved for individuals with functional impairment or chronic disease.

Many patients with pulmonary involvement will not require ED treatment. Simple observation by a primary care physician on an outpatient basis for the development of treatable symptoms or abnormal findings on pulmonary function tests will suffice. Patients seen in the ED with significant dyspnea, functional impairment, and parenchymal disease noted on radiography are candidates for therapy with prednisone, 0.5 to 1 mg/kg/day, if bacterial, mycobacterial, fungal, and neoplastic processes can be excluded. Patients may need specialist consultation, hospital admission, or (at the very least) close outpatient follow-up. Depending on symptomatic response, doses can be tapered over a 6- to 12-month period by the patient’s primary physician.

Musculoskeletal complaints and erythema nodosum are best treated with NSAIDs. Patients with cardiac or neurologic involvement should first undergo standard ED management, with subsequent specialist consultation and consideration given to systemic treatment with glucocorticoids. Invasive interventions such as transvenous cardiac pacing or an intraventricular drain for obstructive hydrocephalus may be required. Ocular manifestations can be treated with topical cycloplegics and, after consultation with an ophthalmologist, topical corticosteroids. Suspected globe perforation as a result of severe keratitis warrants an ophthalmologic evaluation in the ED.

Weekly methotrexate and daily azathioprine are corticosteroid-sparing agents that can be prescribed by a pulmonologist or rheumatologist for steroid-dependent patients. Anti–tumor necrosis factor medication may be a future option in severe cases.^18,19 Tetracyclines are occasionally used for the treatment of skin lesions.^18,20 Radiation therapy and surgical intervention have been used for focal intracranial disease refractory to multiple agents. Lung, heart, or liver transplantation are last-line treatments.

Patient Disposition and Next Steps in Care

The EP should give first consideration to bacterial, mycobacterial, or fungal causes of the patient’s signs and symptoms. Lymphoma and other neoplastic processes are also potential diagnoses. If these entities can be excluded or if patients are known to have sarcoidosis, they may be discharged provided that they are minimally symptomatic. Oral prednisone can be prescribed if needed for control of symptoms. However, close outpatient primary care or rheumatology follow-up is mandatory in all cases.

Most patients with functional impairment and no known history of sarcoidosis will need to be admitted for evaluation of other infectious and neoplastic processes before a definitive diagnosis can be made and treatment started.

Epidemiology

Raynaud phenomenon is a vasospastic disorder marked by minute- to hour-long episodes of digital ischemia on exposure to cold or emotional stress. Up to 20% of the population may suffer from Raynaud phenomenon. Cases commonly involve women and occur in cooler environments.

Pathophysiology

In primary Raynaud phenomenon, the microstructure of distal vessels is entirely normal and symptoms are due to intrinsic hyperreactivity of these vessels when exposed to a trigger. In secondary Raynaud phenomenon, symptoms result from arterial luminal occlusion or stasis of flow, external compression, fibrosis, or abnormal neural innervation.

Presenting Signs and Symptoms

Intense vasoconstriction results in decreased perfusion, well-demarcated pallor, and loss of sensation in the fingers and toes and rarely the nose and ears. With the return of sluggish flow, the extremity turns from white to blue. Paresthesias may be present. Subsequently, with increased flow, the digits become bright red in a phase termed reactive hyperemia. It is during this time of reperfusion that patients will have throbbing pain. Although the triphasic color changes are not always present, it is the predictable response to cold or stress that defines Raynaud phenomenon.

In primary Raynaud phenomenon, the appearance of the vasculature and the patient’s digits is normal between attacks.

In secondary Raynaud phenomenon, the symptoms are not always symmetric. Over time, there may be structural changes in distal vessels and permanent changes in the appearance of the patient’s digits.

Differential Diagnosis and Medical Decision Making

The cardinal stigmata of autoimmune diseases (sclerodermatous skin changes, muscle weakness, rash) may not be present at the time that a patient has symptoms of Raynaud phenomenon (Box 109.5). A diagnosis of primary Raynaud phenomenon is sometimes made on the initial visit when in actuality the patient later turns out to have secondary Raynaud phenomenon caused by an underlying autoimmunity yet to be manifested.

A well-demarcated symmetric change in color occurs during an attack or can be precipitated by placement of the extremity in ice water. Fibrosis, pitting, or ulceration of the fingertips is indicative of the structural vascular and dermal changes in secondary Raynaud phenomenon. In the nail fold capillary examination, immersion oil is placed over the skin at the proximal end of the nail and an ophthalmoscope is used to denote normal-appearing capillaries. Abnormally tortuous, enlarged capillaries or a heterogeneous appearance may be indicative of Raynaud phenomenon secondary to scleroderma, idiopathic inflammatory myopathy, or another vascular disease.

Autoantibodies, cryoglobulins, and serum or urine protein electrophoresis to determine secondary causes of Raynaud phenomenon are not standard parts of the ED work-up.

Treatment

Patients should be instructed to avoid cold and stress, cease tobacco consumption, and wear warm clothing. Oral administration of nifedipine, 10 to 20 mg taken 30 minutes before exposure to cold, can minimize attacks.²¹ Alternatively, patients may take up to 60 mg/day divided into three doses. Once-a-day extended-release tablets are also available. Caution should be used in the elderly and those with cardiac and vascular disease. One study suggested that the angiotensin receptor blocker losartan (50 mg/day) outperforms nifedipine.²² Prazosin (1 to 2 mg three times daily) and topical nitrates are second-line agents for primary Raynaud phenomenon.²³ Endothelin antagonists, phosphodiesterase inhibitors, and intravenous infusions of prostacyclin analogues are newer therapies for severe or secondary Raynaud phenomenon.^22,24 Temporary relief of symptoms can be achieved by chemical sympathectomy via local or regional infiltration of an anesthetic. Surgical treatments, including palmar sympathectomy, thoracoscopic cervical sympathectomy, or arteriolysis (release of fibrotic adventitia), are last-line therapy.

Patient Disposition and Next Steps in Care

Most patients with primary or secondary Raynaud phenomenon may be discharged home for primary care follow-up in the following 2 to 4 weeks.

Admission is occasionally required. In addition to prolonged arteriolar constriction and the occasional limb threat, chest pain can occur as a result of coronary artery vasospasm.