PATHOLOGY.

Few unique pathologic features are associated with SLE. In patients with arthritis, the synovial histopathology tends to be non-specific, with superficial fibrin-like material and local or diffuse cell lining proliferation. Vascular changes include perivascular mononuclear cells, lumen obliteration, enlarged endothelial cells, and thrombi, but fibrinoid necrosis is uncommon. Biopsies of the malar erythema may reveal some minor basal layer abnormalities, as well as immune complex deposits at the dermal-epidermal junction. Discoid skin lesions are characterized by hyperkeratosis, follicular plugging, and more basal cell layer changes, including immune complexes at the dermal-epidermal junction. Pleura and pericardium are infiltrated by mononuclear cells. Lupus pneumonitis is characterized by alveolar wall injury, hemorrhage, and edema; hyaline membrane formation; and immune complex deposits. Coronary arteries often demonstrate premature-onset atherosclerosis. Libman-Sacks endocarditis is characterized by the accumulation of immune complexes, mononuclear cells, hematoxylin bodies, and fibrin and platelet thrombi. Pathologic examination of the spleen often reveals an "onion skin" appearance of the splenic arteries, which is thought to represent healed arteritis.

RENAL DISEASE.

Minimal disease (type IIA mesangial disease) of glomeruli has immune complex deposits only in mesangial cells. Type IIb mesangial nephritis also has mesangial hypercellularity. Focal proliferative nephritis (type III) has segmental proliferation in glomerular tufts and in the mesangium and immune complex deposits in the mesangium and scattered granular deposits in the subendothelial, subepithelial, and intrabasement GBM. Active diffuse proliferative glomerulonephritis (type IV) affects more than 50% of glomeruli with cellular proliferation, necrosis, "wire loops," subendothelial deposits, and hematoxylin bodies. When chronic, the process involves sclerosis, adhesions, crescents, and (tubular) atrophy. Extensive "lumpy and bumpy" deposits of immune complexes are present. In membranous nephritis (type V) diffuse, uniform thickening of the GBM is seen, with a fine granular deposition of immune complexes in the subendothelial region beneath fused foot processes. Tubular degenerative changes with interstitial mononuclear cells are not uncommon. Extensive crescent formation, representing scarring, indicates a poor prognosis.

The brain is notable for the paucity of pathologic changes. Some minor blood vessel abnormalities, an occasional microinfarct, and some perivascular infiltration have been noted.

CLINICAL MANIFESTATIONS.

SLE is highly variable in onset as well as course. The initial symptoms may be non-specific(Table 289-4)and include myalgia, nausea, vomiting, headaches, depression, easy bruising, or more specific symptoms or any combination thereof. These symptoms may be mild or severe, fleeting or persistent.

GENERAL SYMPTOMS.

Fatigue occurs in virtually all patients with SLE. Fatigue may parallel the onset of SLE or its relapse but should be distinguished from the fatigue associated with other factors such as increased workload, sleep disturbance, depression, unhealthful habits, stress, deconditioning, anemia, the use of certain

medications (including prednisone), and any intercurrent disease. Fever is seen in 80% of patients; it is usually episodic. Infections, which occur commonly in SLE patients, must always be considered.

MUSCULOSKELETAL MANIFESTATIONS.

Arthralgia and arthritis have been noted in 95% of patients with SLE. Symptoms tend to be asymmetrical and migratory, with complaints in a particular joint often gone in 1 to 3 days. Fingers, hands, wrists, knees, and less frequently, ankles, elbows, shoulders, and hips are affected. Morning stiffness is generally measured in minutes, in contrast to hours in rheumatoid arthritis. Although joint deformities are considered to be more a feature of rheumatoid arthritis, damage to periarticular tissue can cause flexion deformities, ulnar deviation, soft tissue laxity, and swan neck deformities, particularly in those with long-standing disease who are receiving corticosteroids. Joint erosions are rare. Tenosynovitis is noted in 10 to 13% of patients. Synovial effusions are infrequent and usually small.

Avascular necrosis may occur, especially in the femoral head and less frequently in the humeral head, tibial plateau, and scaphoid naviculare. Involvement is often bilateral. High prednisone dosage, prolonged use, and pulse steroids are risk factors. The first symptom of hip involvement may be groin pain. Radiography may be negative or equivocal, but magnetic resonance imaging (MRI) is usually diagnostic. Osteoporosis is common, especially in trabecular bones, and may not be worsened by corticosteroids. Muscle weakness may represent myositis (uncommon) or be due to medications (corticosteroids, antimalarials). Myalgia is very common.

MUCOCUTANEOUS LESIONS.

Photosensitivity, implying a rash after exposure to UVB light (e.g., sunlight, fluorescent light), occurs in more than 50% of patients. Some patients are also sensitive to UVA light--the clue, rash after exposure to sun filtered through glass. Fair-skinned individuals tend to be more susceptible. Photosensitivity may develop at any time or vary in intensity during the course of SLE. The classic butterfly rash, i.e., erythema over the cheeks and nose, develops after UV exposure in more than 50% of patients. The skin may feel warm and slightly edematous. Application of alcohol, found in many sunscreens, may cause vasodilation and thereby more erythema. The rash may last for hours or days and often recurs. A maculopapular eruption with fine scaling may ensue and last longer, although it generally heals without residue.

Discoid lesions develop in 25% of patients with SLE but may also occur in the absence of any other feature of SLE. Discoid lesions are characterized by discrete round, annular, erythematous, slightly infiltrated plaques covered by a well-formed adherent scale that extends into dilated hair follicles. Follicular plugging is prominent. Lesions slowly expand with active inflammation at the periphery, and in their wake are left depressed scars, telangiectasia, and depigmentation; central scarring with atrophy is characteristic. Lesions tend to occur on the face, scalp, neck, and ears and around the shoulders. Some lesions may be hyperkeratotic and thus be confused with psoriasis. Patients with isolated discoid lupus have about a 10% chance of eventually developing SLE.

Subacute cutaneous lupus erythematosus occurs in about 10% of patients with SLE. The lesions are small, erythematous, slightly scaly papules that evolve into psoriasiform or annular forms. Lesions appear typically on the forearms and upper part of the torso; atrophy or scarring rarely develops, although telangiectasia does. A strong association is seen with HLA-DR3 and anti-Ro antibodies.

Lupus profundus/panniculitis is a rare manifestation of SLE. Typically, painful nodules develop under a skin lesion on the scalp, face, arms, chest, back, thighs, and buttocks and resolve as a depression. Ulcerations are uncommon. The presence of immune complex deposits at the dermal-epidermal junction helps distinguish these lesions from those of the Weber-Christian syndrome. Bullous lesions are rare and can be distinguished from other bullous diseases by the difference in serum antibodies and dermal immune deposits.

Hair loss, on the scalp or elsewhere, occurs in 71% of SLE patients. The most common is premature hair loss (telogen effluvium) characterized by a diffuse thinning of the scalp. Such hair loss may follow a flare of SLE, stress, pregnancy, or the use of steroids; the hair generally grows back. Some patients have "lupus hair," hair that easily fractures and is thin and unruly. Discoid lesions of the scalp usually result in permanent hair loss.

Mucous membranes are frequently affected. Discoid lesions may appear on the lip. The soft or hard palate may be involved by discoid plaques, by areas of erythema, and especially by painful ulcers. These lesions should be distinguished from lichen planus, candidiasis, aphthous stomatitis, bites, leukoplakia, and malignancy--by biopsy. Nasal ulcers have been noted in 20% of patients.