A 28-year-old woman presents to her primary care physician with a 3-month history of fatigue. Her past medical history includes severe acne. She has had 3 uncomplicated vaginal deliveries and has healthy children aged 5, 3, and 2 years. Questioning reveals that she develops an erythematous rash upon minimal sun exposure, and has heavy menstrual periods despite being on oral contraceptives for the past 2 years. For the past 6 months, she has taken minocycline for acne. Physical examination reveals small joint effusions and tenderness to palpation of the knees bilaterally. Lab testing reveals a normocytic anemia, thrombocytopenia, mild hyper-bilirubinemia, and a marked elevation in her ANA titer. Which of the following statements best characterizes this patient’s illness?
This patient likely has drug-induced lupus erythematosus. Minocycline is one of many medications implicated. Other common offenders include procainamide, hydralazine, propylthiouracil, carbamazepine, phenytoin, and isoniazid. Stopping the offending agent is essential and will lead to resolution of the disease in weeks to months. Renal and CNS disease are uncommon in drug-induced lupus; usually skin and joint manifestations predominate. In lupus, immune-mediated hemolysis is the usual cause of the anemia. Although depressed erythropoiesis from anemia of chronic disease (answer a) can contribute to the patient’s low hemoglobin, the elevated bilirubin suggests hemolysis. Likewise, despite the heavy periods from her thrombocytopenia, long-standing iron deficiency anemia (answer b) will cause a low MCV (microcytic anemia). Anti-histone antibodies (answer d) are very common in drug-induced lupus. Answer e is incorrect as patients with lupus (drug-induced or otherwise) have a higher rate of clot formation and may suffer from antiphospholipid antibody syndrome. Although not directly related to venous thromboembolism, long-standing inflammation with lupus accelerates the rate of atherosclerosis, predisposing to arterial occlusive disease over time.
A 42-year-old woman presents to the clinic with a 4-week history of nonproductive cough, progressive dyspnea on exertion, and joint pain. During this time she has developed night sweats and moderate fatigue. She was born in the United States and denies travel outside the country, homelessness, or incarceration. Review of systems highlights the fact that she recently visited an optometrist secondary to blurred vision, but a change in glasses did not improve the symptom. A 5-lb unintentional weight loss is noted in her chart since her last clinic visit 3 months ago. Current vital signs include BP 110/68, HR 88, RR 22, and oxygen saturation 95% on room air. Her lungs are clear, but she has mild peripheral lymphadenopathy, with bilateral supraclavicular and axillary nodes up to 2 cm in size. The nodes are rubbery and nontender. A chest radiograph performed in your office indicates bilateral hilar lymphadenopathy, with a small area of infiltrate in the right upper lobe.
Of the following, which is the best next step in management of this patient?
This patient presents with a likely diagnosis of sarcoidosis. The differential diagnosis includes tuberculosis (made less likely by her paucity of risk factors) and lymphoma. Sarcoidosis affects the lung in over 90% of patients. Although any organ can be affected by sarcoidosis, skin and eye are often involved. Joint involvement occurs in 10% to 20% of patients, usually affecting knees and ankles. The acute arthritis (often associated with hilar lymphadenopathy) is usually self-limited, but the chronic arthritis can be destructive. The diagnosis of sarcoidosis is made through a combination of clinical and pathologic findings. Although there are several other reasonable “best next” approaches to this patient (including clarification of the x-ray findings with a CT scan, performing additional blood work such as a blood count, hemoglobin, peripheral smear, angiotensin-converting enzyme level), biopsy is necessary to establish the diagnosis. Although ACE levels are elevated in 30% to 80% of patients with sarcoidosis, its relatively low sensitivity and specificity prevent this test from replacing the need for pathologic tissue diagnosis. TB skin testing (TST) is an imperfect approach to diagnosis in the setting of concern for active TB. Some patients exhibit anergy with active TB, leading to a false-negative skin test. Many patients will have a positive skin test that reflects latent TB, atypical mycobacterium exposure, or prior BCG vaccination. If active TB is suspected, sputum smears and cultures with patient isolation would be a more appropriate choice than skin testing, although the TST may be a part of that workup. Additionally, answer a is incorrect because the test itself does not assess “active” infection. Although many patients with asymptomatic sarcoidosis can be managed with conservative therapy and close followup (answer c), the diagnosis must be crystallized first. This patient is not asymptomatic; eye, joint, and lung involvement would likely require active treatment. Beginning empiric anti-tuberculos drugs may be an appropriate step (answer d) in the management of active TB, but the patient’s negative risk factors for TB and the presence of bilateral hilar lymphadenopathy (unusual in TB except for those cases associated with AIDS) militate against empiric therapy. Steroids may very well be used in this patient (answer e) if the diagnosis of sarcoidosis is established, but other etiologies such as lymphoma and TB must be ruled out first.
A 32-year-old Japanese woman has a long history of recurrent aphthous oral ulcers. In the last 2 months she has had recurrent genital ulcers. She now presents with a red painful eye that was diagnosed as anterior uveitis. What is the most likely diagnosis?
This patient has classic Behçet disease, which occurs more commonly in Asians. Behçet disease is a multisystem disorder that usually presents with recurrent oral and genital ulcers. One-fourth of patients develop superficial or deep vein thrombophlebitis. Iritis, uveitis, and nondeforming arthritis are common. Blindness, aseptic meningitis, and CNS vasculitis may occur. Rare complications include pulmonary artery aneurysms and GI inflammation which may lead to perforation. Mucocutaneous lesions are usually treated with topical corticosteroids. Immunosuppressive therapy is recommended for patients with threatened blindness or central nervous system disease. The oral lesions of herpes simplex infection occur over the lips; anterior uveitis would be very uncommon. The mucocutaneous lesions of HIV infection are usually caused by Candida and are easily distinguishable from aphthous ulcers. Neither diabetes nor lupus would cause genital ulcers or anterior uveitis.
A 53-year-old man presents with arthritis, cough, hemoptysis, and bloody nasal discharge. Urinalysis reveals 4+ proteinuria, RBCs, and RBC casts. Chest x-ray shows several bilateral cavitary nodules. CT scan of chest is shown below. ANCA is positive in a cytoplasmic pattern. Antiproteinase 3 (PR3) antibodies are present, but antimyeloperoxidase (MPO) antibodies are absent.
Which of the following is the most likely diagnosis?
Wegener granulomatosis (WG) is a granulomatous vasculitis of small- and medium-sized arteries and veins. It affects the lungs, sinuses, nasopharynx, and kidneys, where it causes a focal and segmental glomerulonephritis. Cavitary lung nodules are caused by ischemic necrosis from arterial occlusion. Other organs can also be damaged, including the skin, eyes, and nervous system. Most patients with the disease develop antibodies to certain proteins in the cytoplasm of neutrophils, called antineutrophil cytoplasmic antibodies (ANCA). The most common ANCA staining pattern seen in WG is cytoplasmic, C-ANCA. The C-ANCA pattern is usually caused by antibodies to proteinase-3. A perinuclear pattern, P-ANCA, is sometimes seen. P-ANCA is usually caused by antibodies to myeloperoxidase. Behçet syndrome is not associated with ANCA positivity. Henoch-Schönlein purpura and classic polyarteritis do not involve the upper airways and rarely affect the lungs. Sarcoidosis may involve the upper respiratory tract (20%), but it does not cause bloody nasal discharge, cavitary lung disease, or glomerulonephritis.
A 50-year-old white woman presents with aching and stiffness in the trunk, hip, and shoulders. There is widespread muscle pain after mild exertion. Symptoms are worse in the morning and improve during the day. They are also worsened by stress. The patient is always tired and exhausted. She has trouble sleeping at night. On examination, joints are normal. ESR is normal, and Lyme antibody and HIV test are negative. A diagnosis is best made by which of the following?
The signs and symptoms suggest fibromyalgia. Fibromyalgia is a very common disorder, particularly in middle-aged women, characterized by diffuse musculoskeletal pain, fatigue, and nonrestorative sleep. The American College of Rheumatology has established diagnostic criteria for the disease, which include a history of widespread pain in association with 11 of 18 specific tender point sites. In this patient with very characteristic signs and symptoms, the identification of 11 specific trigger points would be the best method of diagnosis. Polymyalgia rheumatica may sometimes be in the differential diagnosis. In this patient PMR would be unlikely given the normal ESR. Fibromyalgia is distinct from inflammatory muscle disease like polymyositis or dermatomyositis. Patients with inflammatory muscle disease usually present with proximal muscle weakness and elevated muscle enzymes, whereas patients with fibromyalgia usually complain of musculoskeletal pain and have normal muscle enzymes. Muscle pain is less prominent in inflammatory muscle disease. Fibromyalgia has been associated with other somatic syndromes, including irritable bladder, irritable bowel syndrome, headaches, and temporomandibular joint pain. Patients with fibromyalgia have an increased lifetime incidence of psychiatric disorders, particularly depression and panic disorder. However, there is convincing evidence that fibromyalgia is a disease of abnormal central nervous pain processing associated with amplification of nociceptive stimuli. This suggests that lower thresholds for noxious stimuli are caused by a CNS abnormality of as yet undetermined etiology. Psychiatric evaluation would, therefore, be useful only for other psychiatric symptoms, not for diagnosis of fibromyalgia itself. Steroids and NSAIDs have not been shown to be helpful in fibromyalgia, since there is no evidence of inflammation.
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