Porth's Essentials of Pathophysiology, 4e

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Disorders of the Skeletal System: Metabolic and Rheumatic Disorders

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analysis of bloodwork. The most common laboratory test performed is the immunofluorescence test for ANA. The ANA test is not specific for SLE, and positive ANA results may be found in healthy persons or may be associated with other disorders. Other serum tests may reveal moderate to severe anemia, thrombocytopenia, and leukocytosis or leukopenia. Treatment of SLE focuses on managing the acute and chronic symptoms of the disease. 46 Persons with photo- sensitivity should be cautioned against sun exposure and should apply a protective lotion when outdoors. Skin lesions often respond to local application of corticoste- roids and minor joint symptoms are usually relieved by rest and NSAIDs. An antimalarial drug (e.g., hydroxychloroquine) may be helpful in treating mucocutaneous manifestations, pleuritis, arthritis, and fatigue. Corticosteroids are used to treat more significant symptoms of SLE, such as renal and CNS disorders. High-dose corticosteroid treatment is used for acute symptoms, and the drug is tapered to the lowest therapeutic dose as soon as possible to mini- mize the adverse effects. Immunosuppressive drugs, such as azathioprine and cyclophosphamide, may be used in cases resistant to corticosteroids. Biologics, such as rituximab and belimumab, target B cells and are used for refractory symptoms. Systemic Sclerosis/Scleroderma Systemic sclerosis, commonly called scleroderma, is an autoimmune disease of connective tissues that causes extensive fibrosis throughout the body. 47–49 The disease affects women four times as frequently as men, with a peak incidence in the 35- to 50-year-old age group. 47 The cause of systemic sclerosis is poorly understood, although there is evidence of both humoral and cellu- lar immune system abnormalities. 47 Fibroblast activa- tion with excessive fibrosis is a hallmark of the disease. Skin involvement is the usual presenting symptom, but it is the involvement of organs such as the gastrointes- tinal tract, heart, lungs, and kidneys that produces the major morbidity and mortality. Microvascular disease is also present early in the disease, with repeated cycles of endothelial damage followed by platelet activation and release of platelet factors that lead to fibrosis and nar- rowing of the microvasculature and tissue ischemia. Clinical Manifestations. Scleroderma presents as two major clinical subsets: limited and diffuse scleroderma. The most common subset, which accounts for about half of the cases, is limited cutaneous scleroderma in which the skin changes are limited to the fingers, forearms, and face. Some persons with limited involvement also develop a condition called the CREST syndrome, char- acterized by a combination of c alcinosis (i.e., calcium deposits in the subcutaneous tissue that erupt through the skin), R aynaud phenomenon (a vascular disorder characterized by reversible vasospasm of the arteries supplying the fingers [see Chapter 18]), e sophageal dys- motility, s clerodactyly (localized scleroderma of the fin- gers), and t elangiectasia (dilated skin capillaries). 48

Diffuse scleroderma, which accounts for approxi- mately 35% of persons with scleroderma, is charac- terized by severe, widespread, and progressive skin involvement and early onset of organ involvement. 49 The typical person has a “stone facies” due to tight- ening of the facial skin with restricted motion of the mouth. Other cutaneous manifestations include hair loss on the involved skin and telangiectasis on the face, buccal mucosa, chest, and hands. Almost all persons with diffuse scleroderma develop Raynaud phenom- enon. Musculoskeletal involvement is common. Puffy hands with arthralgia and myalgia may lead to diffi- culty forming a fist. There are palpable or audible fric- tion rubs over the extensor and flexor tendons of the hands, knees, and ankles. Involvement of the esopha- gus that leads to difficulty swallowing is common, and malabsorption may develop if the disease affects the intestine. Pulmonary involvement leads to dyspnea and eventually respiratory failure. Vascular involvement of the kidneys is responsible for malignant hyperten- sion and progressive renal insufficiency. Cardiac prob- lems include pericarditis, heart block, and myocardial fibrosis. Treatment. Treatment of systemic sclerosis is largely symptomatic and supportive. 48,49 Advances in treat- ment, primarily the use of angiotensin-converting enzyme (ACE) inhibitors in renal involvement, have led to a substantial decrease in the mortality from hyper- tensive renal disease. 50 Cardiopulmonary manifestations of scleroderma, specifically pulmonary hypertension, can be treated with prostanoids (or endothelial recep- tor antagonists [bosentan]). Disease modifying agents such as methotrexate, cyclophosphamide, azathioprine, and mycophenalate mofetil have been reported effective in limited case series or randomized controlled trials. These agents can be used in early diffuse disease. Seronegative Spondyloarthropathies The spondyloarthropathies are an interrelated group of multisystem inflammatory disorders that primar- ily affect the axial skeleton, particularly the spine. 3,4,51 Sacroiliitis is a pathologic hallmark of the disorders. Typically, the inflammation begins at sites, called enthe- se s, where tendons and ligaments insert into bone rather than the synovium. There may also be inflammation and involvement of the peripheral joints, in which case the signs and symptoms overlap with other inflammatory types of arthritis. The spondyloarthropathies are grouped into two subtypes: the axial spondyloarthropies, which include ankylosing spondylitis; and the peripheral spondylo- arthropathies, which include psoriatic arthritis, reac- tive arthritis, inflammatory bowel disease–associated arthritis, and undifferentiated peripheral spondyloar- thritis. Although they differ in terms of factors such as age and type of onset and extent of joint involvement, there is clinical evidence of overlap between the various disorders.