SYSTEMIC SCLEROSIS (SCLERODERMA)
This is a connective tissue disorder characterized by diffuse fibrosis. Females are affected more often than males and the incidence of disease increases during the fifth through sixth decades of life. The degree of involvement may vary from limited disease of the skin to widespread diffuse fibrosis with visceral involvement. Diffuse cutaneous involvement refers to rapidly progressive widespread skin fibrosis which may involve the distal and proximal extremities plus the trunk. Patients with diffuse cutaneous involvement have a greater propensity to progress towards visceral involvement as compared to patients with limited cutaneous involvement. Limited cutaneous involvement refers to disease which is limited to the fingers and face, and this form of disease is associated with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) and has a more prolonged disease course. Systemic sclerosis sine scleroderma refers to an infrequently occurring form of the disease which is characterized by visceral involvement without the characteristic cutaneous manifestation. Criteria have been established to aid in diagnosis.
Patients often present with Raynaud's phenomenon, swelling of the fingers or polyarthritis of the small joints of the hands. Several months after the initial complaints, patients often develop the characteristic skin changes (increased thickness, loss of skin folds, shiny taut skin, and either hyper- or hypopigmentation). Skin changes of the digits, dorsum of the hands, face, and trunk is strongly suggestive of systemic sclerosis (verses scleredema if scleroderma specific antibodies are all absent) and rarely occurs with other disorders. When skin changes are limited to the extremities, the differential includes diabetic cheirarthropathy (seen in poorly controlled diabetics and characterized by a positive prayers sign) and eosinophilic fasciitis (consider when there is associated peripheral eosinophilia and hypergammaglobulinemia). It is of note that Raynauds phenomenon is almost universally present in cases of limited cutaneous disease, and it is generally the initial complaint preceding other symptoms by years or decades. In contrast, Raynauds phenomenon is present at diagnosis in only 75% of patients with diffuse scleroderma, and its absence in these patients indicates an increased risk for renal involvement.
Other symptoms are numerous reflecting the diffuse involvement of this disease and include:
JOINTS: Polyarthralgia may involve both small and large joints. Arthralgia is often an early manifestation.
SKELETAL MUSCLE: Diffuse atrophy and decreased range of motion are common.
Distal esophageal motor dysfunction often manifests as dysphagia. When there is involvement of the lower esophageal sphincter, gastroesophageal reflux commonly occurs. An esophagram performed in the supine position often demonstrates decreased motility. Less commonly, involvement of the small intestine may manifest as malabsorption with resultant diarrhea, pneumatosis cystoides intestinalis (air in the wall of the intestine), chronic intestinal pseudo-obstruction, telangiectasia, and diverticula. Pseudo-obstruction is associated with decreased or absent activity on manometry and symptoms may respond to prokinetic therapy with either erythromycin elixir or octreotide. Diarrhea secondary to bacterial overgrowth may respond to cyclic courses of antibiotics. Pneumatosis cystoides intestinalis must be differentiated from more serious conditions requiring surgical intervention; however, once the diagnosis is secured a conservative approach may be employed with intravenous alimentation and antibiotics. Primary biliary cirrhosis may be associated with limited cutaneous systemic sclerosis (CREST syndrome).
Clinical symptoms are uncommon in both forms of diseases; however, when present they are seen almost entirely in patients with diffuse scleroderma. Involvement most commonly manifests as congestive heart failure, and arrhythmias (both atrial and ventricular).
Involvement may manifest as bibasilar linear or nodular interstitial fibrosis noted on chest radiographs. These radiographic abnormalities are often accompanied by a reduced DLCO and evidence of restrictive airway disease on pulmonary function testing. The frequency and severity of pulmonary symptoms are increased in patients who are positive for antitopoisomerase I antibody and decreased in patients who are positive for anticentromere antibody. Patients with limited cutaneous disease may manifest pulmonary involvement as isolated pulmonary hypertension. Pulmonary malignancies, pleurisy, pneumothorax, and silicosis are also seen with an increased frequency in scleroderma patients. Studies suggest that cyclophosphamide therapy may improve pulmonary function in afflicted patients.
Involvement may manifest as hypertension, azotemia, and microscopic hematuria or proteinuria. Scleroderma renal crisis affects approximately 25% of patients with diffuse disease (this complication is rare in patients with limited disease) and manifests as malignant arterial hypertension and oliguric acute renal failure, which may be associated with volume overload. Renal crisis is also associated with microangiopathic hemolytic anemia and thrombocytopenia. Angiotensin converting enzyme inhibitor therapy should be administered to patients with renal manifestations. Severe renal disease should be treated with hemodialysis as indicated by the circumstances of each case.
Malignancies to include breast cancer, lung cancer and non-Hodgkin's lymphoma are seen with increased frequency in persons afflicted with this disorder.
Laboratory abnormalities are uncommon on basic screening labs. Most patients are antinuclear antibody (ANA) positive, and the diagnosis of scleroderma should be questioned in patients who are ANA negative. The anticentromere pattern for ANA screening is highly indicative of systemic sclerosis as is anti-topoisomerase I (formerly Scl-70) autoantibodies. The CREST syndrome (limited cutaneous disease) is strongly associated with the presence of the anticentromere pattern; whereas, the presence of anti-topoisomerase I autoantibodies indicates a strong probability for diffuse cutaneous disease.
There is currently no effective therapy for cure. Consultation weith a rheumatologist is prudent. ACEI's or ARB's are helpful in treating renal complications and hypertension. Severe renal dysfunction may require hemodialysis. As mentioned, manifestations of individual organ systems should be closely monitored and therapy offered as they arise.