XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 278 antibody synthesis by B lymphocytes. In humans, they have the property of forming ro- settes with sheep erythrocytes (E-rosettes), and they lack readily detectable immunoglob- ulin of any class on their membranes. Although the maturation of T cells is thymus- dependent, the cells arise from precursors in bone marrow. T cells constitute about 70 to 80% of blood lymphocytes; they comprise greater than three-quarters of thymus lympho- cytes but less than one-quarter of bone marrow lymphocytes. In lymph nodes, they are found in paracortical areas. Specific monoclonal antibodies have been developed to char- acterize various subsets of T cells — cells that carry a CD4ϩ surface antigen are helper cells, and those with a CD8ϩ antigen function as cytotoxic-suppressor cells. Antibody- dependent cell-mediated cytotoxicity is a property of a class of non-B, non-T lymphocytes called large granular lymphocytes (LGL cells). Antibody-dependent cell-mediated cyto- toxicity can also be mediated by monocyte-macrophages and neutrophils. XI-42. The answer is E. (Chap. 311) Although most clinicians believe that women with SLE should not become pregnant if they have active disease or advanced renal or cardiac disease, the presence of SLE itself is not an absolute contraindication to pregnancy. The outcome of pregnancy is best for those women in remission at the time of conception. Even in women with quiescent disease, exacerbations may occur (usually in the first tri- mester and in the immediate postpartum period), and 25 to 40% of pregnancies end in spontaneous abortion. Fetal loss rates are higher in patients with lupus anticoagulant or anticardiolipin antibodies. Flare-ups should be anticipated and vigorously treated with steroids. Steroids given throughout pregnancy also usually have no adverse effects on the child. In the case presented, the fact that the woman had a life-threatening bout of disease a year ago would argue against stopping her drugs at this time. Neonatal lupus, which is manifested by thrombocytopenia, rash, and heart block, is rare but can occur in mothers with anti-Ro antibodies. XI-43. The answer is C. (Chap. 305) Immunoglobulin A is the predominant immunoglobulin in body secretions (IgG is predominant in serum). Each secretory IgA molecule is a dimer consisting of a secretory component and a J chain. The secretory component, a protein of molecular weight 70,000, is synthesized by epithelial cells and facilitates IgA transport across mucosal tissues. The J chain is a small glycopeptide that aids the polymerization of immunoglobulins. IgA exists as two subclasses: IgA1 (75% of the total) and IgA2 (25% but more prevalent in secretions). IgA provides defense against local infections in the respiratory, gastrointestinal, and genitourinary tracts, and prevents access of foreign sub- stances to the general systemic immune system. It also can prevent virus binding to epi- thelial cells. IgM, not IgA, is the principal immunoglobulin in the primary immune re- sponse and is the usual antibody in cold agglutinins. The half-life of IgA is about 6 days; IgE has the shortest half-life, approximately 2 to 2.5 days. XI-44. The answer is E. (Chap. 314) Sjo¨gren’s syndrome, an autoimmune destruction of the exocrine glands, can be primary or it can occur in association with rheumatoid arthritis, SLE, or systemic sclerosis. A mononuclear cell infiltrate, which can be seen in virtually any organ, is pathognomonic if found in the salivary gland in association with keratocon- junctivitis sicca (conjunctival and corneal dryness) and xerostomia (lack of salivation). Since minor salivary glands will be obtained in a lip biopsy, such a procedure can be diagnostic. Severe dryness of the mouth can lead to an increased incidence of dental caries. Corneal dryness may be severe enough to result in ulceration. The most common form of renal involvement (seen in 40% of patients with primary Sjo¨gren’s) is an interstitial ne- phritis resulting in renal tubular acidosis. Hypersensitivity vasculitis, manifested by pal- pable purpura of the lower extremities, is not uncommon. Sensory neuropathies, interstitial pneumonitis, and autoimmune thyroid disease may also accompany primary Sjo¨gren’s syndrome. Finally, pseudolymphoma, characterized by lymphadenopathy and enlargement of the parotid gland, and frank non-Hodgkin’s lymphoma may occur. Cardiac disease is very rare in Sjo¨gren’s syndrome. XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 279 XI-45. The answer is E. (Chap. 309) The differential diagnosis of myopathy in an AIDS patient is vast and includes infection, zidovudine-induced myositis, vasculitis, and poly- myositis. Electromyography would likely show similar findings in all of these conditions. Blood cultures may be useful if the etiology is infectious, but generally are of little benefit in further narrowing the differential diagnosis. Similarly, lymph node biopsy may detect specific infections or malignant processes, but will not necessarily determine the etiology of the myopathy. Discontinuing the zidovudine, a drug which can cause myositis, will aid in determining the diagnosis only in zidovudine-induced myopathy. Muscle biopsy is the procedure best suited to establish a definitive diagnosis. XI-46. The answer is B. (Chap. 306. Klein, Sato, N Engl J Med 343:702–709, 2000.) The human MHC, also known as the human leukocyte antigen (HLA) complex, is a 4-Mb region on chromosome 6 that is packed with genes including those encoding HLA class I and class II molecules, which are involved in the immunologic specificity. Class I genes produce polymorphic proteins that bind to a ␤ -microglobulin peptide-binding groove. The 2 class II peptide complex is recognized by CD4ϩ T cells. Class I genes are expressed in all nucleated cells, although to a higher degree in leukocytes. Class II genes are expressed on myeloid cells and can be induced by stimuli such as inflammatory cytokines, e.g., interferon ␥ . Certain HLA types are associated with susceptibility to specific infectious diseases such as tuberculosis and leprosy or with resistance to malaria. There are now many examples of specific HLA alleles being associated with susceptibility to certain immunologically mediated diseases such as Behc¸et’s syndrome and ankylosing spondylitis. Though HLA-B27 is very highly associated with ankylosing spondylitis, there is little evidence for any molecular role for the gene product in the disease. XI-47. The answer is B. (Chap. 322. Perez-Ruiz at al; Nephron 86:287–291, 2000.) Indi- cations for chronic hypouricemic therapy include recurrent attacks of gouty arthritis, hy- peruricemia refractory to diet and weight reduction, elevated urinary uric acid, and uric acid stones. The uricosuric agent probenicid is indicated only if the baseline urinary uric acid excretion is normal. Allopurinol is safe and effective in the setting of chronic renal failure. It should be used with care in patients taking thiazide diuretics due to the increased incidence of rash. Colchicine prophylaxis can be initiated in a patient with frequent epi- sodes of gout who is receiving allopurinal (which can exacerbate an attack). The non- steroidal anti-inflammatory agents, whether cyclooxygenase-2-specific or not, do not have a role as prophylactic agents. XI-48. The answer is C. (Chap. 324. Gladman, Rheum Dis Clin North Am 24:829–844, 1998.) There are three main varieties of psoriatic arthritis (an inflammatory arthritis affecting 5 to 42% of patients with psoriasis): asymmetric inflammatory arthritis, symmetric arthritis [more common in women, usually in the hands, similar to rheumatoid arthritis (RA), but without nodules], and psoriatic spondylitis. The pathology is similar to that seen in RA (early neutrophil and later monocytic synovial infiltration). There are no characteristic laboratory abnormalities in patients with psoriatic arthritis, but radiographs, if they reveal features unique to this disease relative to RA, may be diagnostically helpful. Such special features include the pencil-in-cup appearance of the distal terminal phalanx due to cuplike erosions and bony proliferation with tapering of the proximal phalanx; proliferation of the bone near osseous erosions, terminal phalyngeal osteolyis, bone proliferation and perios- titis, and telescoping of one bone into another (opera-glass deformity). Inflammation of the tendons and ligaments (ethesopathy) is also characteristic. Nonsteroidal anti-inflam- matory agents are the therapeutic mainstays; sulfasalazine or methotrexate is often required in difficult cases. XI-49. The answer is D. (Chap. 323. Zimmerli et al, JAMA 279: 1537 – 1541, 1998.) If an infection in a prosthetic joint is documented after joint aspiration, cure usually requires a combination of organism-specific antibiotic plus joint replacement. There is, however, an XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 280 emerging literature documenting that a nonsurgical cure of staphylococcal infections may be possible with a prolonged course of rifampin plus ciprofloxacin, each given orally. Prevention of prosthetic joint infections via perioperative antibiotic prophylaxis, laminar intraoperative airflow, and aggressive treatment of extraarticular infections in the postop- erative period is the best approach. Infectious complications of joint replacement surgery occur in 1 to 4% of patients and include acute infections with Staphylococcus aureus, streptococci, or enteric gram-negative rod bacteria as well as more indolent infections presenting much later (and in a more subtle fashion) caused by coagulase-negative strep- tococci or diptheroids. XI-50. The answer is B. (Chap. 323. Cucurull, Espinoza, Rheum Dis Clin North Am 24:305– 322, 1998.) Gonococcal arthritis is the most common infectious arthritis in young pa- tients and particularly affects pregnant or menstruating women who have asymptomatic carriage of the organism in the urethra, cervix, or pharynx. A monarticular “septic arthritis” picture is rare. A migratory polyarthritis and/or tenosynovitis of distal joints associated with fever, chills, and a characteristic pustular rash on the trunk and extremities represents the classic clinical syndrome. Blood cultures are almost always negative, and joint aspi- ration is often difficult and generally yields a bland culture and gram-negative formula. It is most useful to culture the skin lesions or mucosal sites [in specialized medium (Thayer- Martin agar, rapidly transported to the laboratory in a 5% CO atmosphere)]. Due to the 2 frequency of penicillin-resistant gonococci, treatment with ceftriaxone should be initiated, pending culture results. XI-51. The answer is D. (Chap. 326) This patient has typical adhesive capsulitis of the left shoulder, also known as “frozen shoulder.” This condition develops in older women, many of whom have comorbid conditions such as chronic lung disease, diabetes, or coronary artery disease. An injury may initiate a sequence of events, beginning with lack of move- ment and ending with immobility and osteopenia on radiography. The diagnosis may be confirmed at arthroscopy if only a limited amount (Ͻ15 mL) of contrast fluid can be injected into the joint. Improvement may be spontaneous, but physical therapy to mobilize the joint is often helpful. Therapy in difficult cases may include forceful injection of contrast to lyse adhesions or manipulation under anesthesia. XI-52. The answer is B. (Chap. 325) Fibromyalgia is characterized by widespread muscu- loskeletal pain, stiffness, paresthesia, nonrestorative sleep, and easy fatigability associated with multiple tender points, which are widely and symmetrically distributed. Fibromyalgia is more prevalent in women. Several causative mechanisms for fibromyalgia have been postulated. Disturbed sleep has been implicated as a factor in the pathogenesis. Many patients fit a psychiatric diagnosis, the most common being depression, anxiety, somati- zation, and hypochondriases. There is disagreement about whether some of these abnor- malities may represent reactions to chronic pain or if fibromyalgia is a reflection of psy- chiatric disturbance. However, fibromyalgia also occurs in patients without psychiatric diagnoses. Patients may complain of joint pain and perceive their joints are swollen; how- ever, joint examination is normal. Glucocorticoids have little benefit and should not be used. Other therapies include local measures, biofeedback, anxiolytics, and antidepres- sants. XI-53. The answer is D. (Chaps. 323, 202) The patient has desert fever, a syndrome caused by coccidioidomycosis infection, which is endemic in the southwest United States. This syndrome is largely an acute hypersensitivity reaction to the primary pulmonary infection, which is symptomatic in only 40% of affected persons. Manifestations of hypersensitivity may include erythema nodosum, erythema multiforme, arthralgia, arthritis, conjunctivitis, and episcleritis. However, disseminated coccidioidomycosis may occur during the primary infection and could result in osteomyelitis (which may seed an adjacent synovium directly), fungal arthritis, skin lesions, or CNS disease. Even in the case of hematogenously derived joint infection, synovial fluid cultures will rarely be positive; synovial biopsy for culture XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 281 and histology may be required. Serologic tests, while possibly acutely negative in a patient with primary pulmonary infection only, can be quite helpful, particularly when there is disseminated involvement. XI-54. The answer is D. (Chap. 305) T cell precursors leave the yolk sac, fetal liver, or bone marrow and migrate to the thymus, where they undergo further maturation. Even before T cell receptor gene rearrangements occur, pre-T cells express the CD7 antigen, the earliest marker of T cell lineage. After the CD2 adhesion molecule, which functions as the receptor for sheep red blood cells, is expressed on the cell surface, assembly of the T cell receptor complex begins. This complex consists of the five proteins that make up the CD3 signal transduction moiety plus the two antigen-recognizing heterodimer molecules that form the actual T cell antigen receptor. The proteins that can function as part of the T cell antigen receptor all have a variable (produced by V-J recombination) and constant region and bear homology to the immunoglobulin heavy and light chains. Along with the histocompati- bility proteins and the CD2, CD4, and CD8 molecules, the T cell antigen receptor chains are members of the immunoglobulin gene superfamily, which provides the immunologic diversity required to distinguish self from nonself and recognize an inordinate number of foreign antigens. After CD3 T cell receptor expression, but before suppressor or helper phenotype is determined, there is a thymic stage wherein both CD4 and CD8 antigens are expressed. Some lymphoblastic lymphomas arise at this stage of T cell development. XI-55. The answer is B. (Chap. 308. Buckley, N Engl J Med 325:110, 1991.) Isolated IgA deficiency is the most common immunodeficiency disorder, with an incidence between 1:600 and 1:800. Affected persons have a normal or reduced number of B cells with surface IgA, but seem to have overabundant immature cells that coexpress IgA and IgM, sug- gesting a block in B cell terminal differentiation. This presumption is substantiated by in vitro studies showing that lymphocytes from IgA-deficient persons can synthesize but are unable to secrete IgA. Both serum IgA and secretory IgA usually are reduced. Although IgA deficiency need not be associated with clinical disease, it frequently is. Recurrent sinopulmonary infection is most common. Allergy occurs with an incidence of 1:200 to 1:400, compared with 1:600 to 1:800 in the general population. Approximately 30 to 40% of IgA-deficient persons have antibodies directed against IgA, thus predisposing them to anaphylactoid reactions following the infusion of blood products unless the blood is ob- tained from IgA-deficient donors. Persons with isolated IgA deficiency are also at greater risk for developing autoimmune diseases, including lupus and rheumatoid arthritis. Im- munoglobulin treatment will not restore IgA levels to normal and is of little value in this condition. XI-56. The answer is C. (Chap. 305) Most antigen-antibody complexes are cleared by cells of the reticuloendothelial system. It appears that in some conditions the reticuloendothelial system can be overwhelmed by immune complexes, thereby impeding the removal and leading to the deposition of immune complexes. Deposition of these complexes in tissues other than those of the reticuloendothelial system is responsible for the signs and symptoms of immune-complex disease. In animal models, the persistence of complexes is necessary for the development of renal disease; also, slight antigen excess has been found to predis- pose to the formation of antigen-antibody complexes, which persist in the circulation and lead to inflammatory illness. Immune complex-mediated vascular damage can lead to cutaneous necrotizing vasculitis. Electron microscopy reveals subendothelial immune com- plexes that presumably incite an array of inflammatory cells to migrate toward the vessel. XI-57. The answer is D. (Chap. 306) Class I HLA antigens are encoded at the A, B, and C loci of the human major histocompatibility complex on chromosome 6. Each such antigen consists of an 11.5-kDa ␤ -microglobulin subunit (also encoded in the HLA region) and 2 a 44-kDa chain with three separate domains that contain the antigenic specificity. Only certain areas of the heavy chain are diverse, so individual molecules share Ͼ80% sequence homology. Class I molecules are expressed on all cells except mature red blood cells. XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 282 These antigens are defined serologically and are useful in predicting results for organ transplants. Because class I antigens are not distributed evenly from one racial group to another, it can be more difficult for a person of African descent, for example, to procure a bone marrow donor from a registry where most of the potential donors descend from Northern Europe. XI-58. The answer is D. (Chap. 319) This patient has many of the hallmarks of systemic amyloidosis. An abdominal fat pad aspirate or a rectal biopsy is the best way to make the diagnosis, although biopsy of any affected organ may be carried out. A positive Congo red histologic stain helps to establish the diagnosis. The classification of amyloid protein fibrils that are deposited in the tissues is based on their biochemical type. AL amyloid residues bear homology to immunoglobulin light chains and are seen in de novo or my- eloma-associated disease. The AA type of amyloid, made up of a protein of 76 amino acids, is seen secondary to a host of chronic inflammatory conditions, including long- standing rheumatoid arthritis, tuberculosis, bronchiectasis, familial Mediterranean fever, and leprosy. Other types of amyloid proteins are seen in familial amyloid polyneuropathy, medullary carcinoma of the thyroid, and Alzheimer’s disease (the beta, or A4, protein). Amyloidosis should be suspected in any patient with an underlying chronic inflammatory disease who develops hepatomegaly, splenomegaly, malabsorption, cardiac disease, or proteinuria. Cardiac disease usually consists of congestive heart failure with low QRS- complex voltage, arrhythmias, and exquisite sensitivity to digitalis. Waxy papules or plaques in the axillary folds may signal the deposition of amyloid in the skin; purpura after minor trauma is not uncommon. Gastrointestinal problems caused by amyloid include macroglossia, malabsorption, and bleeding. In addition to amyloid-induced synovitis, pe- ripheral neuropathy and carpal tunnel syndrome may be seen. XI-59. The answer is E. (Chap. 311) The most common cause of drug-induced SLE is pro- cainamide, which produces a positive ANA in 75% of those who take it and a 20% incidence of clinical lupus. In contrast, hydralazine induces an ANA in 25% and a clinical lupus syndrome in 10%. Slow acetylators seem to have more problems with drug-induced autoimmune phenomena. Though up to 50% of those with drug-induced lupus have ar- thralgias, pleuropericarditis, or both, renal disease is rare. In an effort to distinguish drug- induced lupus (which should last Ͻ6 months) from de novo lupus (a disease uniquely positive for anti-dsDNA and anti-Sm), a complete ANA panel should be sent. Most patients will respond initially to withdrawal of the offending drug; if not, then a brief trial of steroids is indicated. XI-60. The answer is A. (Chap. 325) Relapsing polychrondritis is an uncommon disorder affecting middle-aged individuals characterized by progressive episodes of inflammation of various cartilaginous structures, especially the ears, nose, and laryngotracheal tree. About 30% have an associated rheumatologic disorder, but others have other conditions such as inflammatory bowel disease, primary biliary cirrhosis, or myelodysplasia. Addi- tional clinical features may include scleritis, neurosensory hearing loss, polyarthritis, vas- culitis, cardiac abnormalities, skin lesions, and glomerulonephritis. Although the under- lying pathophysiologic basis for this disease is unclear, there is an association with the HLA-DR4 allele and with antibodies to type II collagen. There is evidence for an auto- immune lymphocytic reaction against cartilage matrix protein. The diagnosis is generally made on clinical grounds, although a cartilage biopsy would be confirmatory. Patients with Wegener’s granulomatosis could also have nasal and bronchial tree involvement but have granulatomous inflammation (unlike relapsing polychrondritis patients) and do not have auricular involvement. Antineutrophil and immune complexes have also been noted in this disease, but they are not pathognomonic. XI-61. The answer is D. (Chap. 318) Sarcoidosis is a systemic granulomatous inflammatory disorder that frequently involves the lungs, where it causes a typical interstitial lung disease that may be asymptomatic, may cause transient respiratory difficulties with or without hilar XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 283 adenopathy, or may progress to end-stage pulmonary fibrosis. Extrapulmonary sarcoidosis may involve the eyes, skin, liver, bones, gastrointestinal tract, kidneys, nervous system, and heart. In the United States, 10 to 20% of cases consist of asymptomatic hilar adenop- athy detected on chest radiographs taken for other reasons; these cases may constitute a higher fraction of the total in other countries where routine preemployment chest radiog- raphy is more widely practiced. The disease occurs more frequently among blacks than whites by a substantial margin. At sites of disease activity, such as the lung, there is an accumulation of activated helper-inducer (CD4ϩ) lymphocytes, with release of immuno- logic mediators such as IL-2 and interferon ␥ , and resultant granuloma formation. In contrast to other interstitial lung diseases, the diagnosis may frequently be made by the demonstration of the characteristic granulomatous inflammation in tissue obtained by trans- bronchial biopsy. Prognosis depends on the risk of progression to advanced pulmonary fibrosis, and those persons with intense pulmonary inflammation may benefit from treat- ment with glucocorticoids. Chest radiography and pulmonary function testing cannot dis- tinguish accurately between active inflammation and established fibrosis; hence, most cli- nicians familiar with the disease utilize procedures such as bronchoalveolar lavage or gallium-67 scanning, or both, to assess the intensity of the alveolitis present. These pro- cedures may be performed serially during the course of the patient’s illness to follow the progress of the disease and response to therapy. XI-62. The answer is C. (Chap. 312) Rheumatoid factors are antibodies to the Fc fragment of immunoglobulin G. They may be of the IgG, IgA, or IgM class; the widely used latex and sheep-cell agglutination tests detect rheumatoid factors primarily of the IgM class. Chronic antigenic stimulation is one of the processes important in the production of rheu- matoid factors. Rheumatoid factors are associated not only with rheumatoid arthritis and other autoimmune diseases but also with lymphoreticular malignancies and chronic infec- tions, such as subacute bacterial endocarditis. Rheumatoid factors are usually present within the first year of onset of rheumatoid arthritis; their presence correlates with the extraarticular manifestations of the disease. Patients with rheumatoid arthritis who have positive serologic tests for IgM rheumatoid factor have a worse prognosis than those who are seronegative. XI-63. The answer is A. (Chap. 312) Joint stiffness in the morning or after periods of inac- tivitylastingmorethan1hischaracteristic of inflammatory rheumatic disease. Arthritis characteristic of rheumatoid arthritis is persistent, remaining in the same joints for months. Migratory arthritis, in which short-lived arthritis symptoms in one joint subside as symp- toms begin in another joint, is not characteristic of rheumatoid arthritis. Persons who have rheumatoid arthritis can have involvement of the cervical spine, the wrist joints, and all the small joints of the hand except the distal interphalangeal joints. Wrist-joint arthritis can lead to median-nerve entrapment (carpal tunnel syndrome). XI-64. The answer is C. (Chap. 315) This patient has an acute inflammatory asymmetric polyarthritis associated with ocular (conjunctivitis, occasionally anterior uveitis) and cu- taneous (keratoderma blennorhagicum on palms and soles; circinate balanitis on the glans penis) disease. Moreover, he has had a recent episode of urethritis, possibly caused by Chlamydia. He therefore has so-called reactive arthritis, also known as Reiter’s syndrome. This entity can follow certain infectious illnesses, most notably dysentery or venereal disease usually in patients who are HLA-B27-positive. The constitutional symptoms as- sociated with the acute illness can be severe. The ESR is frequently elevated. Sacroiliitis and spondyloarthropathy may be seen as late sequelae. Patients will respond to nonsteroidal agents, but there is little evidence to support the benefit of antibiotics, other than in erad- icating chlamydia, if present. XI-65. The answer is B. (Chap. 317. Hoffman, Ann Intern Med 116:488–498, 1992.) This patient presents with findings characteristic of Wegener’s granulomatosis. Sinus disease (manifested by bloody or purulent nasal discharge), pulmonary disease, and glomerulo- XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 284 nephritis are seen in greater than 80 percent of affected patients. Sinus involvement would be unlikely in Goodpasture’s syndrome, which is associated with anti-basement membrane antibodies. Other findings characteristic of Wegener’s include ocular involvement, skin lesions, and nervous system manifestations (including cranial neuritis or mononeuritis multiplex), as well as elevated ESR, anemia, leukocytosis, and hypergammaglobulinemia. The diagnosis can be made by finding necrotizing granulomatous vasculitis in an involved site. Although the immunopathogenesis of this entity is unclear, antibodies to a neutrophil protein (found in the azurophilic granules) can be frequently found. The disease can be successfully treated in over 90 percent of patients with the use of glucocorticoids and cyclophosphamide. The glucocorticoids are gradually tapered and the cyclophosphamide, the mainstay of treatment, should be continued for about 1 year after complete remission. XI-66. The answer is E. (Chap. 318) While 10 to 20% of patients with sarcoidosis present with asymptomatic disease found incidentally on chest x-ray and 40 to 70% have the characteristic insidious development of disease, the remainder present over the span of a few weeks. Constitutional and respiratory symptoms dominate the acute presentation. Two distinct patterns of acute sarcoidosis are recognized. Lofgren’s syndrome, seen in Scan- dinavian, Irish, and Puerto Rican females, is characterized by erythema nodosum, arthral- gias, and bilateral hilar lymphadenopathy. The constellation of findings in the Heerfordt- Waldenstrom syndrome consists of fever, parotid enlargement, anterior uveitis, and facial nerve palsy. Interstitial pulmonary involvement would be rare in acute sarcoidosis. My- opathy and skin lesions are most consistent with dermatomyositis. Although 5% of patients with sarcoidosis have cardiac abnormalities, valvular heart disease — other than occasional instances of papillary muscle dysfunction — is rare. XI-67. The answer is B. (Chap. 317) Patients with midline granuloma, characterized by local inflammation and destructive mutilation of head and neck tissues, may present with nasal and sinus symptoms. Ulcerations of the nasal septum and soft and hard palates are har- bingers of very destructive processes in any area in the neck or above. Granulomatous infiltration and necrosis will be noted on pathologic examination of the involved areas. Radiation therapy is the treatment of choice and is successful in averting the almost cer- tainly fatal course in untreated patients. Midline granuloma can be difficult to distinguish from cocaine-induced septal perforation, malignant lymphoma, and a host of chronic in- fections including histoplasmosis, blastomycosis, coccidioidomycosis, leprosy, tubercu- losis, syphilis, and leishmaniasis. While Wegener’s granulomatosis is associated with sim- ilar upper airway findings, the absence of vasculitis on biopsy, the absence of pulmonary and renal disease, and the presence of palatal perforation make the diagnosis of midline granuloma much more likely. Midline granuloma never involves structures below the neck. XI-68. The answer is E. (Chaps. 320, 323. Baker, N Engl J Med 329:1013–1020, 1993.) The analysis of synovial fluid begins at the bedside. When fluid is withdrawn from a joint into a syringe, its clarity and color should be assessed. Cloudiness or turbidity is caused by the scattering of light as it is reflected off particles in the fluid; these particles are usually white blood cells, although crystals may also be present. The viscosity of synovial fluid is due to its hyaluronate content. In inflammatory joint disease, synovial fluid contains enzymes that break down hyaluronate and reduce fluid viscosity. In contrast, synovial fluid taken from a joint in a person with degenerative joint disease, a noninflammatory condition, would be expected to be clear and have good viscosity. The color of the fluid can indicate recent or old hemorrhage into the joint space. Pigmented villonodular synovitis is asso- ciated with noninflammatory fluid that is dark brown in color (“crankcase oil”) as a result of repeated hemorrhage into the joint. Gout and calcium pyrophosphate deposition disease produce inflammatory synovial effusions, which are cloudy and watery. In addition, these disorders may be diagnosed by identification of crystals in the fluid— sodium urate crystals of gout are needle-like and strongly negatively birefringent, whereas calcium pyrophos- phate crystals are rhomboidal and weakly positively birefringent. XI. D ISORDERS OF THE I MMUNE S YSTEM, C ONNECTIVE T ISSUE, AND J OINTS — A NSWERS 285 XI-69. The answer is B. (Chap. 325) Neuropathic joint disease, or “Charcot’s foot,” may develop in about 0.5% of patients with diabetes (formerly most commonly seen in ad- vanced syphilis). The pathophysiology of this destructive process may represent a com- bination of autonomic dysfunction leading to increased blood flow with bone resorption plus loss of proprioception resulting in damage from repetitive traumas. The disease can be difficult to distinguish clinically and radiologically from severe osteoarthritis, with bony loss and osteophytes being noted in radiographs in each condition. The ankle joints are most commonly affected; patients often give a history of some initiating trauma. The joint is often swollen, and in the case of ankle involvement, collapse of the tarsal bones may lead to a concave sole, or “rocker foot.” The diagnosis is made clinically and after oste- omyelitis, osteoarthritis, and calcium pyrophosphate deposition disease are excluded. Treatment includes no weight-bearing; stabilization of the foot, usually with a brace (fol- lowed carefully due to the neuropathy); and sometimes surgical joint fusion. XI-70. The answer is D. (Chap. 325) This patient has classic nail clubbing, or hypertrophic osteoarthropathy, which can occur as a primary disease process but is mainly secondary to other conditions such as severe pulmonary infections, congenital heart disease, and, most notably, lung cancer, where it occurs in 5 to 10% of patients. The bone changes include periostitis followed by new bone formation and cortical thickening with prolifer- ation of nearby connective tissue, which gives the nails their clubbed appearance and accounts for sponginess of the nail bed. Pain, sometimes associated with synovial effusions in the ankles, wrist, and knees, can occur. Although once thought to be due to elaboration of a protein or prostaglandin, recent studies suggest a role for platelet clumps, which, upon interaction with the endothelium in the distal extremities, result in the local release of substances capable of eliciting proliferation of connective tissue and periosteum such as platelet-derived growth factor and transforming growth factor ␤ . Optimal treatment in- cludes reversal of the underlying disease process if possible; nerve block may be needed if symptoms are severe. XI-71. The answer is B. (Chap. 312. Klippel, N Engl J Med 343:1640–1641, 2000.) The synovium in patients with RA is characterized by lymphocytic infiltration (CD4ϩ and CD8ϩ T cells) and fibroblast proliferation and notable for the presence of a host of proin- flammatory cytokines secreted by activated immune and supporting cells. Moreover, neu- trophils migrate into the synovial fluid. One or more of these events, perhaps mainly IL- 1 and tumor necrosis factor (TNF) secretion, stimulate collagen breakdown, which leads to the bone and cartilage destruction associated with chronic RA. Moreover, systemic secretion of TNF- ␣ may account for the constitutional symptoms of malaise and fatigue typical in RA patients. Therefore, agents that neutralize TNF- ␣ such as the type II TNF- ␣ receptor fused to an immunoglobulin (etenercept) and a humanized monoclonal anti- TNF- ␣ antibody (infliximab) have been considered for use in RA. Recent studies have demonstrated that these agents control signs and symptoms in RA patients that have failed disease-modifying antirheumatic drugs such as methotrexate, gold, D -penicillamine, the antimalarials, and sulfasalizine. Serious infections may be more likely in patients receiving an anti-TNF- ␣ drug, and their long-term impact on the natural history of RA has not yet been determined, although recent studies do suggest that their use may limit joint damage compared with methotrexate. Immunosuppressive drugs such as cyclosporine may occa- sionally be effective, but they are often associated with unacceptable side effects. This page intentionally left blank. 287 XII. ENDOCRINE AND METABOLIC DISORDERS QUESTIONS DIRECTIONS: Each question below contains five suggested responses. Choose the one best response to each question. XII-1. The use of repeated phlebotomy in the treatment of persons with symptomatic hemochromatosis may be ex- pected to result in (A) increased skin pigmentation (B) improved cardiac function (C) return of secondary sex characteristics (D) decreased joint pain (E) an unchanged 5-year survival rate XII-2. A 19-year-old man has had a 5-year history of hy- perglycemic episodes and glycosuria. However, he has never been hospitalized for diabetic ketoacidosis. Which of the following statements regarding the mode of inher- itance of his disease is correct? (A) This disease is inherited in an autosomal recessive fashion. (B) If the patient has children, they will have approxi- mately a 50% chance of developing diabetes. (C) The diabetic susceptibility gene in this patient re- sides on human chromosome 6. (D) The patient is likely to carry one of a limited num- ber of HLA-D locus alleles. (E) The patient has an unusual susceptibility to a viral infection. XII-3. Which of the following studies is most sensitive for detecting diabetic nephropathy? (A) Serum creatinine level (B) Creatinine clearance (C) Urine albumin (D) Glucose tolerance test (E) Ultrasonography XII-4. Which of the following statements concerning in- tensive insulin therapy for diabetes (the use of an external insulin pump or three or more daily insulin injections guided by frequent blood glucose monitoring) is correct? (A) All patients with diabetes mellitus should receive such therapy. XII-4. (Continued) (B) It has been definitively shown that compared with standard therapy, such intensive therapy reduces the likelihood of retinopathy in patients with insu- lin-dependent diabetes mellitus. (C) Such therapy will consistently return blood glucose to normal levels, but a reduction of long-term complications has not been demonstrated. (D) With careful monitoring, an increase in the number of hypoglycemic episodes is avoided. (E) Intensive insulin therapy failed to reduce the level of glycosylated hemoglobin. XII-5. Evidence of continuing ovarian estrogen production in a 29-year-old woman who is being evaluated for sec- ondary amenorrhea is provided by (A) normal plasma estrone and luteinizing hormone (LH) levels (B) a normal plasma prolactin level (C) an increase in plasma estradiol level after the ad- ministration of human chorionic gonadotropin (hCG) (D) the appearance of menses after a short course of progesterone therapy (E) a lack of hot flashes XII-6. Which of the following inhibits growth hormone secretion from the anterior pituitary gland? (A) Somatostatin (B) Growth hormone – releasing hormone (GHRH) (C) Hypoglycemia (D) Arginine (E) Serotonin XII-7. A 7-year-old girl is referred for evaluation of vagi- nal bleeding for 2 months. The mother says that she has not been exposed to exogenous estrogens. Physical ex- amination reveals height at the 98th percentile, Tanner stage III breast development, and no axillary or pubic hair. No abdominal or pelvic masses are palpated. Neurologic Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use. [...]... measured at 8. 16 mmol/L (147 mg/dL) Endocrine studies reveal a TSH of 0.07 mU/L, a total thyroxine of 87 nmol/L (6 .8 ␮g/dL), a total triiodothyronine of 1.1 nmol/L (70 ng/dL), a prolactin levels of 3.3 ␮g/L (3.3 ng/mL), ␣-subunit level of Ͻ0.2, follicle-stimulating hormone (FSH) level of 3.3 IU/L, a fasting serum cortisol level of 690 nmol/L (2.5 ␮g/dL), and a 60-min postadministration of cosyntropin... rate is 75 mm/h A serum sodium level of 1 28 mmol/L 294 XII ENDOCRINE AND METABOLIC DISORDERS — QUESTIONS XII-49 (Continued) (1 28 meq/L) and a potassium level of 4.2 mmol/L (4.2 meq/L) are noted A serum osmolality of 265 (mosmol/kg of water), total cholesterol of 7.7 mmol/L (2 98 mg/dL), LDL cholesterol level of 4.7 mmol/L ( 181 mg/dL), and a HDL cholesterol level of 1.2 mmol/L (46 mg/dL) are noted Her... XII- 58 Which of the following conditions is characteristic of the presentation of osteomalacia in adults? (A) (B) (C) (D) (E) Bowing of the tibia Pseudofractures Increased thickness of the epiphyseal growth plate Hypocalcemia Hyperphosphatemia XII-59 A 61-year-old woman noticed severe sharp pain in her back after lifting a suitcase A compression fracture of the T11 vertebral body is identified on x-ray... two-step testing procedure will limit the number of full glucose tolerant tests performed The screening test is typically given as a 50-g 1-h glucose challenge test The 50-g oral glucose challenge test is meant as a screening test A serum glucose cut-off point of Ն7.7 mmol/L (140 mg/dL) has a sensitivity of 80 % A more stringent cut-off at 7.2 mmol/L (130 mg/dL) is associated with a sensitivity of. .. plasmacytoma Paget’s disease of bone osteomalacia XII- 48 The most important regulator 1,25(OH)2 vitamin D concentration is (A) (B) (C) (D) (E) of serum serum calcium serum magnesium serum 25(OH) vitamin D parathyroid hormone prolactin XII-49 A 63-year-old woman presents to your clinic complaining of a 4- to 5-month history of anorexia, fatigue, and visual disturbances She has a long history of hyperlipidemia... pg/mL), a 24-h urinary calcium is 2 68 mg, and a serum alkaline phosphatase level is 106 U/L The patient has no history of orthopedic fractures or nephrolithiasis A bone densitometry study is performed that reveals a lumbar spine z-score of Ϫ0 .86 , a femoral neck zscore of Ϫ1.34, and a radius z-score of Ϫ1.42 A parathyroidectomy is likely to result in which of the following? (A) Normalization of the serum... Hypogammaglobulinemia XII-20 The most likely etiology for the eating disorder anorexia nervosa is (A) decreased levels of luteinizing hormone – releasing hormone (LHRH) (B) decreased levels of growth hormone (C) decreased levels of insulin-like growth factor I (somatomedin C) (D) low levels of serum thyroxine (E) psychiatric disorder XII-21 A 45-year-old obese man without known medical problems complains of feeling... apoprotein CII will exhibit which of the following abnormalities? (A) Excessive chylomicronemia (B) Excessive amounts of LDL in serum (C) Excessive amounts of very low density lipoprotein in serum (D) Excessive amounts of chylomicron remnant (E) Excessive amounts of intermediate-density lipoproteins XII-40 A 32-year-old man sustains a myocardial infarction He relates a history of early myocardial infarctions... is the result of (A) autonomous adrenal production of steroids (B) autonomous pituitary production of ACTH (C) extraglandular formation from large amounts of nonadrogenic adrenal steroids (D) failure of production of an adrenal product necessary for negative feedback on pituitary ACTH secretion (E) positive feedback on pituitary ACTH secretion by abnormal adrenal products XII-42 A 3 8- year-old woman with... is referred for endocrinologic evaluation of possible cortisol excess The woman receives a midnight dose of 1 mg of dexamethasone; a plasma cortisol level drawn at 8 A.M the next day is 386 nmol/L (14 ␮g/ dL) At this point in the evaluation the most appropriate diagnostic maneuver would be (A) CT scanning of the pituitary gland (B) abdominal CT scanning (C) measurement of 24-h 17-hydroxycorticosteroid . performed that re- veals a lumbar spine z-score of Ϫ0 .86 , a femoral neck z- score of Ϫ1.34, and a radius z-score of Ϫ1.42. A para- thyroidectomy is likely to result in which of the follow- ing? (A). measurement of 24-h 17-hydroxycorticosteroid ex- cretion in urine (D) measurement of a 24-h urine free cortisol (E) a 2-day high-dose dexamethasone suppression test (2.0 mg every 6 h for 48 h) XII. E NDOCRINE. prolactin XII-49. A 63-year-old woman presents to your clinic com- plaining of a 4- to 5-month history of anorexia, fatigue, and visual disturbances. She has a long history of hyper- lipidemia