The following cases and commentary, which focus on rheumatology, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 18). MKSAP 18 Part A was released this summer. Part B will be released in print on Dec. 31, 2018, and in digital format on Jan. 31, 2019.
Case 1: Hip pain and inability to stand
A 72-year-old man is evaluated in the emergency department after falling when his leg gave way as he tried to arise from bed. He has left hip pain, with the inability to stand and pain at rest. He was recently diagnosed with lymphoma, for which he is receiving chemotherapy. History is significant for a left hip replacement 7 years ago for osteoarthritis. His chemotherapy regimen consists of rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone.
On physical examination, temperature is 38.2 °C (100.8 °F); other vital signs are normal. The right upper chest is implanted with a venous access port. Warmth and tenderness around the left hip are noted. Pain in the groin is noted. There is limitation of motion in all directions on both active and passive range of motion of the left hip. There are no other joint abnormalities.
Laboratory studies show an erythrocyte sedimentation rate of 73 mm/h, a leukocyte count of 13,400/µL (13.4 × 109/L), and a serum urate level of 8.2 mg/dL (0.48 mmol/L).
Left hip radiographs show periprosthetic lucency.
Which of the following is the most likely diagnosis?
A. Gout flare
C. Hip dislocation
D. Prosthetic joint infection
Case 2: Swelling in an intubated patient
A 55-year-old man is hospitalized for acute respiratory failure requiring intubation and mechanical ventilation. He also has increasing leg swelling with nonhealing skin ulcers on the legs for the past 4 weeks, and pain with swelling of the bilateral wrists and finger joints for the past 6 weeks. He quit smoking 15 years ago. History is otherwise unremarkable. Prior to hospitalization he was taking no medications.
On physical examination, temperature is 37.2 °C (99.0 °F), blood pressure is 150/95 mm Hg, pulse rate is 110/min, respiration rate is 20/min (ventilator set rate, 14/min), and oxygen saturation is 92% on FiO2 of 40%. There is blood in the endotracheal tube. Lung crackles are heard bilaterally. Swelling of the wrists, metacarpophalangeal joints, and proximal interphalangeal joints is noted. Two necrotic ulcers on the left leg and one necrotic ulcer on the right leg are present. There is 2+ pitting edema of the legs.
Laboratory studies show normal C3, C4, and rheumatoid factor; negative antinuclear antibodies; positive ANCA with a perinuclear pattern; and 3+ protein on urinalysis. Blood and sputum cultures are negative.
Chest radiograph shows diffuse bilateral infiltrates. Biopsy of a skin ulcer shows nongranulomatous, necrotizing small-vessel vasculitis with immunofluorescence negative for immune complexes.
Which of the following is the most likely diagnosis?
A. Granulomatosis with polyangiitis
B. IgA vasculitis
C. Microscopic polyangiitis
D. Rheumatoid vasculitis
E. Thromboangiitis obliterans
Case 3: GI bleeding with systemic sclerosis
A 43-year-old man is evaluated in the emergency department for gastrointestinal bleeding. He reports loose, dark stools of 2 weeks' duration. He has an 8-year history of diffuse cutaneous systemic sclerosis (DcSSc) complicated by Raynaud phenomenon and gastroesophageal reflux disease. He does not drink alcohol or take NSAIDs. His only medication is omeprazole.
On physical examination, temperature is normal, blood pressure is 100/60 mm Hg, pulse rate is 80/min, respiration rate is 16/min, and oxygen saturation is 94% breathing ambient air. Skin changes associated with DcSSc are noted from the hands to the elbows in the upper extremities and from the feet to the knees in the lower extremities. The abdomen is nontender to palpation. The remainder of the physical examination is normal.
Laboratory studies show a normal chemistry panel and a hematocrit level of 26%.
Upper gastrointestinal endoscopy demonstrates linear ectatic vessels resembling the stripes found on a watermelon that arise from the pylorus. There is no evidence of a hiatal hernia or other abnormal findings.
Which of the following is the most likely diagnosis?
A. Cameron lesions
B. Dieulafoy lesions
C. Gastric antral vascular ectasia
D. Portal hypertensive gastropathy
Case 4: Gout treatment
A 76-year-old man is evaluated for fever and a swollen, painful left knee. He was hospitalized 7 days ago for heart failure and appropriately treated. However, he developed fevers up to 38.0 °C (100.4 °F). On examination, lungs were clear to auscultation. The left knee was hot and swollen; 60 mL of turbid fluid was drained from the knee. Gram stain of the synovial fluid was negative; microscopy revealed needle-shaped intracellular crystals. Gout was diagnosed and the knee was drained again, followed by an injection of 80 mg of methylprednisolone, without improvement. Intravenous methylprednisolone, 60 mg/d for 3 days, did not improve the knee or the fevers. History is also significant for hypertension and gout. Other medications are furosemide, lisinopril, metoprolol, subcutaneous heparin, and morphine as needed.
On physical examination today, temperature is 38.0 °C (100.4 °F), blood pressure is 148/92 mm Hg, pulse rate is 116/min, and oxygen saturation is 97% on ambient air. The left knee is warm, swollen, and tender.
Blood, urine, and synovial fluid cultures are negative.
Which of the following is the most appropriate treatment for the knee?
Case 5: Lupus and cough
A 26-year-old man is hospitalized for a 1-week history of dry cough and progressive shortness of breath. He has a 2-year history of systemic lupus erythematosus (SLE); disease manifestations have been pleuropericarditis, polyarthritis, leukopenia, and nephritis. He currently reports no fever, sputum production, or hemoptysis, as well as no other SLE manifestations. His disease has been difficult to control and has needed multiple tapering doses of prednisone. He currently takes 15 mg/d of prednisone; other medications are hydroxychloroquine and azathioprine.
On physical examination, temperature is 36.4 °C (97.6 °F), blood pressure is 150/100 mm Hg, pulse rate is 98/min, respiration rate is 30/min, and oxygen saturation is 84% breathing ambient air. Diffuse crackles are heard on auscultation of the chest. Diffuse tenderness and swelling of multiple small joints of the hands are present. The remainder of the physical examination is normal.
Laboratory studies show erythrocyte sedimentation rate 68 mm/h, hematocrit 42%, leukocyte count 5500/µL (5.5 × 109/L) with normal differential, creatinine 0.6 mg/dL (53 µmol/L), and low complements (C3 and C4). C-reactive protein and procalcitonin levels are normal.
Chest radiograph and CT scan of the chest show diffuse infiltrates in both lungs with ground glass opacities in multiple lobes. Bronchoalveolar lavage shows only increased leukocytes with lymphocytic predominance. Cultures are pending.
Which of the following is the most likely diagnosis?
A. Acute lupus pneumonitis
B. Acute pulmonary hypertension
C. Community-acquired pneumonia
D. Diffuse alveolar hemorrhage
E. Shrinking lung syndrome
Answers and commentary
Correct answer: D. Prosthetic joint infection.
Prosthetic joint infection is the most likely diagnosis. This patient has a prosthetic hip and is currently undergoing chemotherapy. Malignancy and immunosuppression are risk factors for prosthetic joint infection, and this patient also has a central venous catheter that increases his risk for bacteremia. The elevated leukocyte count and erythrocyte sedimentation rate, along with periprosthetic lucency on radiographs, are all suggestive of prosthetic joint infection. Prosthetic joint infections are divided into early onset (<3 months after placement), delayed (3 to 24 months postsurgery), and late onset (>24 months after placement). Early and delayed infections are usually related to surgical contamination at the time of the implantation, whereas late infections result from hematogenous seeding of the joint. Early and late prosthetic joint infections typically present with pain, warmth, effusion, and fever. Staphylococcus aureus is a leading causative agent in prosthetic joint infections; treatment involves prompt intravenous antibiotics and sometimes removal of the prosthesis.
Gout flare may also cause joint pain and loss of mobility, as well as fever, elevated leukocyte count, and inflammatory markers. However, this patient has no prior history of gout, and the hip is an uncommon place for a gout flare, especially an initial flare. Most initial gout flares affect the foot and/or ankle joints.
Hemarthrosis causes bleeding into a joint and is characterized by pain, swelling, warmth, and impaired mobility. It is diagnosed by synovial fluid aspiration. This patient does not have a history or findings suggestive of a bleeding diathesis to put him at risk for a traumatic hemarthrosis.
A patient with hip dislocation may present in a similar manner as one with prosthetic joint infection, namely pain and difficulty moving the joint; however, a dislocation would be evident on radiographs.
- Both early and late prosthetic joint infections are typically characterized by pain, warmth, effusion, and fever; treatment involves prompt intravenous antibiotics and possible removal of the prosthesis.
Correct answer: C. Microscopic polyangiitis.
The most likely diagnosis is microscopic polyangiitis (MPA), which characteristically affects the lungs and kidneys, along with other organ systems. Diagnosis is suspected based upon typical clinical findings and positive ANCA. The diagnostic gold standard is a biopsy demonstrating nongranulomatous necrotizing pauci-immune vasculitis of small vessels or pauci-immune necrotizing crescentic glomerulonephritis in the kidney. This patient has pulmonary hemorrhage, pauci-immune small-vessel necrotizing vasculitis of the skin, proteinuria, inflammatory arthritis, and a positive p-ANCA (directed against myeloperoxidase)—all consistent with the diagnosis of MPA.
Granulomatosis with polyangiitis (GPA) can cause the same lung, skin, joint, and kidney findings but is usually associated with a positive c-ANCA (directed against proteinase-3). Furthermore, GPA causes granulomatous inflammation; absence of granulomas distinguishes MPA from GPA.
IgA vasculitis (Henoch-Schönlein purpura) can affect lungs, skin, joints, and kidneys but it is an immune complex–mediated vasculitis with deposition of IgA containing immune complexes identified on biopsy, which is not present in this patient.
Rheumatoid vasculitis usually occurs in long-standing disease with positive rheumatoid factor and is immune complex mediated, none of which is present in this patient.
Thromboangiitis obliterans is a smoking-related vasculopathy affecting small to medium vessels with inflammation and thrombosis of vessels in upper and lower limbs, leading to reduced pulses and gangrenous ulcers. This diagnosis is unlikely because this patient no longer smokes, and has involvement of internal organs in addition to the legs.
- The diagnostic gold standard of microscopic polyangiitis is a biopsy demonstrating nongranulomatous necrotizing pauci-immune vasculitis of small vessels or pauci-immune necrotizing crescentic glomerulonephritis in the kidney.
Correct answer: C. Gastric antral vascular ectasia.
The most likely diagnosis is gastric antral vascular ectasia (GAVE) associated with systemic sclerosis. GAVE is the proliferation of blood vessels typically in the antrum of the stomach; on endoscopy, it has the appearance of watermelon stripes (watermelon stomach). Approximately 60% of patients with GAVE have an underlying autoimmune disease; the remainder have portal hypertension secondary to hepatic cirrhosis. GAVE can be a source of both acute and chronic gastrointestinal bleeding. First-line therapy is argon plasma coagulation or laser coagulation.
Cameron lesions are erosions found on the crest of gastric folds within a large hiatal hernia and are thought to be caused by mechanical trauma as the hiatal hernia slides up and down. Up to 5% of patients with known hiatal hernias may have Cameron lesions. There is no evidence of a hiatal hernia, making this diagnosis unlikely.
Dieulafoy lesions are submucosal arterioles that intermittently protrude through the mucosa and cause hemorrhage. Dieulafoy lesions are of unknown etiology and account for about 2% of all causes of acute upper gastrointestinal bleeding and are located in the proximal stomach along the lesser curvature. When bleeding they appear as an isolated pumping arteriole in the absence of a mass or ulcer. The patient's findings do not match those of Dieulafoy lesions.
Portal hypertensive gastropathy (PHG) commonly occurs with advanced cirrhosis and has a characteristic mosaic appearance on endoscopy, most often seen in the body and fundus. It can be confused with GAVE. This patient has no history of cirrhosis or findings to suggest chronic liver disease, making PHG an unlikely diagnosis.
- Patients with diffuse cutaneous systemic sclerosis are at risk for acute and chronic gastrointestinal bleeding secondary to gastric antral vascular ectasia.
Correct answer: A. Anakinra.
Anakinra is the most appropriate treatment for this patient's knee. He has a persistent fever due to a severe acute gouty attack. Synovial fluid analysis permits definitive diagnosis and can rule out other conditions. Under polarized light, monosodium urate crystals are needle shaped and negatively birefringent. Whereas extracellular crystals confirm a chronic gout diagnosis, crystals within neutrophils define active, gout-induced inflammation. Even in the setting of acute gout, Gram stain and cultures must be obtained to exclude infection because acute gout and joint infection occasionally coexist. This patient has not responded favorably to glucocorticoid therapy, which characterizes some severe acute episodes. In a case such as this, an interleukin-1 inhibitor such as anakinra should be provided as a reliable (although expensive) off-label treatment.
Colchicine is unlikely to be effective for an established attack of greater than 12 to 24 hours' duration. It is also unlikely to be useful when intravenous and intra-articular glucocorticoids have been ineffective.
The absence of a response to intra-articular or intravenous glucocorticoids necessitates an alternative treatment; however, NSAIDs would not be as effective as the two previously provided failed alternatives. Additionally, NSAIDs have numerous side effects that might be even more likely to occur during critical illness, and they are relatively contraindicated in a patient with heart failure.
Blood, urine, and synovial fluid cultures have all been negative, the pneumonia is resolving, and there is no clinical evidence of infection. Vancomycin for methicillin-resistant staphylococcus is unnecessary.
- For patients with severe and refractory gouty attacks or with contraindications to other treatments, off-label use of interleukin-1 inhibitors (anakinra or canakinumab) can be considered.
Correct answer: A. Acute lupus pneumonitis.
Acute lupus pneumonitis is the most likely diagnosis in this patient who has difficult-to-control systemic lupus erythematosus (SLE) requiring aggressive therapy with prednisone and azathioprine. Lupus pneumonitis is a rare but severe presentation of SLE characterized by shortness of breath, hypoxia, and diffuse pulmonary infiltrates. Other major entities in the differential diagnosis include infection and diffuse alveolar hemorrhage. He has clear evidence of active SLE with polyarthritis, a high erythrocyte sedimentation rate, hypocomplementemia, and diffuse pulmonary infiltrates on radiologic studies, as well as lymphocytic predominance on bronchoalveolar lavage. These findings are very suggestive of lupus pneumonitis. It usually requires rapid and aggressive therapy with glucocorticoids and/or immunosuppressive agents.
Pulmonary hypertension does not present with diffuse infiltrates with ground glass opacities, as seen in this patient, and it cannot explain the bronchoalveolar lavage findings.
This patient has no fever or sputum production, and testing shows a normal leukocyte count and differential, normal C-reactive protein (CRP), and normal procalcitonin, making infection less likely. CRP is a marker of inflammation, and levels are significantly increased in bacterial pneumonia but frequently normal or only slightly elevated in SLE flares. Procalcitonin is produced by cells as a response to bacterial toxins, which result in serum procalcitonin elevations in bacterial infections.
The patient reports no hemoptysis, and lack of anemia and absence of erythrocytes on bronchoalveolar lavage exclude a diagnosis of diffuse alveolar hemorrhage.
Shrinking lung syndrome presents with chronic insidious shortness of breath with low lung volumes possibly related to diaphragmatic dysfunction. This patient's acute presentation and diffuse infiltrates on imaging is not consistent with this syndrome.
- Lupus pneumonitis is a rare but severe presentation of systemic lupus erythematosus characterized by shortness of breath, hypoxia, and diffuse pulmonary infiltrates.