Cases from MedStar Washington Hospital Center

Cryoglobulinemic vasculitis, goiter, Chagas disease, and more.


Case 1: Cryoglobulinemic vasculitis

By Ana Kavtaradze, MD, ACP Member; Michael Cardis, MD; and Kosuke Yasukawa, MD, FACP

The patient

Figure 1 Purpuric lesions and ecchymosis on thighs and lower legs
Figure 1. Purpuric lesions and ecchymosis on thighs and lower legs.

A 54-year-old woman with a history of liver cirrhosis secondary to hepatitis C virus (HCV) infection (successfully treated with ledipasvir/sofosbuvir five years previously) presented with a rash on her lower extremities. She had noted small, mild pruritic red lesions on her thighs and lower legs bilaterally two days prior to presentation. She reported a similar rash two years previously, which was diagnosed as presumed cellulitis at another medical facility. On presentation, she was afebrile. Physical examination was notable for nonpalpable, minimally tender, purpuric lesions and ecchymosis of the thighs and lower legs (Figure 1).

Figure 2 Skin biopsy showing extravasated red blood cells red arrow and interstitial inflammatory cells black arrows
Figure 2. Skin biopsy showing extravasated red blood cells (red arrow) and interstitial inflammatory cells (black arrows).

Laboratory studies were significant for leukopenia and thrombocytopenia, normal liver enzymes, and elevations in erythrocyte sedimentation rate (ESR) at 33 mm/h (reference range, 0 to 22 mm/h) and C-reactive protein (CRP) level at 30.30 mg/L (reference range, 0.00 to 3.00 mg/L). Additional laboratory studies demonstrated positive cryoglobulins, a C3 complement level of 88 mg/dL (reference range, 90 to 180 mg/dL), a C4 complement level of less than 6.0 mg/dL (reference range, 10 to 40 mg/dL), elevated rheumatoid factor level of 190 IU/mL (reference range, 0 to 15 IU/mL), and undetectable hepatitis C viral load. Antinuclear antibody (ANA), anti-double-stranded DNA, antineutrophil cytoplasmic antibodies (ANCA), anti-cyclic citrullinated peptide, 60-kDa Sjögren's syndrome A/anti-Sjögren's syndrome B (SSA/SSB), serum and urine protein electrophoresis, and HIV tests were all negative. Skin biopsy was significant for extravasated red blood cells and interstitial inflammatory cells suggestive of evolving leukocytoclastic vasculitis (Figure 2). The patient was started on prednisone, 60 mg/d, which was slowly tapered over the next few weeks. Two months after discharge, she was seen in the rheumatology clinic and the rash had resolved.

The diagnosis

The diagnosis is HCV-associated mixed cryoglobulinemic vasculitis. Cryoglobulinemia can be categorized into three types based on immunochemical analysis. In type I, the cryoglobulins are monoclonal immunoglobulins (Ig) linked to a B-cell lymphoproliferative disorder. Type II cryoglobulinemia is characterized by the presence of monoclonal Ig (usually IgM) with rheumatoid factor activity mixed with polyclonal IgG and is associated with HCV, hepatitis B, HIV, autoimmune diseases, and lymphoproliferative disorders. Type III consists of a mixture of polyclonal IgM with rheumatoid factor activity and polyclonal IgG, occurring in secondary autoimmune disorders and some infections such as HCV. Chronic HCV infection accounts for two-thirds of cases of mixed cryoglobulinemia (type II and III). The disease presents in various ways, ranging from purpura and arthralgia to fulminant life-threatening complications such as glomerulonephritis and widespread vasculitis. Skin is the most frequently involved organ.

Diagnosis of mixed cryoglobulinemia is based upon a detailed patient history and examination, presence of cryoglobulins, low complement levels (especially low C4), and presence of rheumatoid factor (positive in 80% to 90% of cases). HCV-associated mixed cryoglobulinemic vasculitis generally responds to antiviral therapy, and a corticosteroid may help to control minor inflammation. However, there are reported cases of persistent mixed cryoglobulinemia and relapse of vasculitis despite sustained virologic response after antiviral therapy, such as that seen in our patient. There are several hypotheses regarding the persistence of vasculitis, including delayed clearance of circulating cryoglobulins and incomplete suppression of B-cell clonal proliferation driving cryoglobulin production, but the exact mechanism is unknown. Anti-CD20 monoclonal antibody may be considered in patients with severe vasculitis or persistent symptomatic cryoglobulinemia.

Pearls

  • Cryoglobulinemic vasculitis should be considered in patients with a history of HCV infection presenting with purpura, even those with a sustained virologic response following antiviral therapy.
  • Anti-CD20 monoclonal antibody may be considered in patients with persistent symptomatic cryoglobulinemia.

Case 2: Massive goiter

By Caroline Argyros, PA-C; Rosemarie Rollins, MD, FACP; and Kosuke Yasukawa, MD, FACP

The patient

A 70-year-old man who had recently arrived from Ethiopia with a history of asthma, type 2 diabetes, obesity, and goiter presented with acute-on-chronic shortness of breath for the past three days. He reported progressive dyspnea and difficulty swallowing over the previous eight years. On presentation, he was tachycardic and tachypneic with oxygen saturation of 90% on room air. Physical examination revealed a large neck mass. The patient had 2+ bilateral pitting lower-extremity edema. A portable chest X-ray indicated pulmonary venous congestion. Transthoracic echocardiogram showed systolic dysfunction with an ejection fraction of 25%.

Figure 3 CT showing severely enlarged thyroid with the right lobe extending retrosternally to the level of the left brachiocephalic vein
Figure 3. CT showing severely enlarged thyroid with the right lobe extending retrosternally to the level of the left brachiocephalic vein.

The patient was started on IV diuresis for suspected congestive heart failure exacerbation. He continued to have shortness of breath and hypoxia to 85% with any exertion, requiring nasal supplemental oxygen at 3 L/min. A contrast CT of the chest was negative for any acute pulmonary findings or pulmonary edema. A CT of the neck revealed a severely enlarged thyroid (right lobe measuring 7.5 cm × 15 cm × 4.5 cm, an isthmus measuring 4.5 cm, and a left lobe measuring 6.3 cm × 5.2 cm × 9.4 cm with the right lobe extending retrosternally to the level of the left brachiocephalic vein) with tracheal narrowing (Figure 3). His thyroid function tests were unremarkable. Fine-needle aspiration showed an adenomatoid nodule. The patient had a total thyroidectomy including removal of the substernal component with the resected specimen weighing 767 g (normal range, 10 to 20 g). The pathology report showed adenomatoid nodules. Postoperatively, he was started on levothyroxine for hypothyroidism.

The diagnosis

This patient was diagnosed with nontoxic multinodular goiter. Worldwide, the most common cause of a goiter is dietary iodine deficiency. Iodine deficiency leads to a compensatory increase in the serum levels of thyroid-stimulating hormone (TSH), leading to hypertrophy and hyperplasia of thyroid follicular cells. However, serum TSH levels have been found to progressively decrease with increasing goiter size, which is likely why this patient was euthyroid. Goiters can be diffuse or multinodular. Most long-standing diffuse nontoxic (simple) goiters due to iodine deficiency progress to multinodular goiters. In the U.S., where iodine deficiency is rare, common causes of goiter include Hashimoto's thyroiditis, Graves' disease, and multinodular goiter not related to iodine deficiency.

The clinical manifestations of goiter depend on thyroid dysfunction and the size and location of the goiter. In the absence of thyroid dysfunction, a goiter is often asymptomatic for a long period of time and may be treated with observation. If there is a concern of malignancy or compressive symptoms, surgery is recommended. Compressive symptoms include exertional dyspnea (most common), cough, wheezing, stridor, choking sensation, dysphagia, phrenic nerve paralysis, or Horner's syndrome. In some cases, facial plethora can be observed with bilateral arm elevation due to thoracic inlet obstruction (Pemberton's sign).

Pearls

  • Extrinsic airway compression due to goiter should be considered in patients with gradually worsening dyspnea.
  • Compressive symptoms of goiter include exertional dyspnea, stridor, wheezing, cough, choking sensation, dysphagia, and hoarseness.

Case 3: Ischemia due to superior mesenteric artery stenosis

By Jennie Zhang, DO, and Kosuke Yasukawa, MD, FACP

The patient

A 68-year-old woman with a history of chronic obstructive pulmonary disease, peripheral artery disease, and metastatic ovarian cancer (treated with cytoreduction surgery and chemotherapy) presented with one day of severe cramping abdominal pain and three days of nausea and decreased oral intake. She had been seen three days prior in the ED for nausea, vomiting, and decreased oral intake. An abdominal CT had not shown any obvious acute intra-abdominal pathology, so she was discharged home.

Figure 4 CT of the abdomen demonstrating severe atherosclerosis of the superior mesenteric artery arrow in transverse section
Figure 4. CT of the abdomen demonstrating severe atherosclerosis of the superior mesenteric artery (arrow) in transverse section.
Figure 5 CT of the abdomen demonstrating severe atherosclerosis of the superior mesenteric artery arrow in sagittal section
Figure 5. CT of the abdomen demonstrating severe atherosclerosis of the superior mesenteric artery (arrow) in sagittal section.

On this presentation, physical examination revealed diffuse tenderness, most prominent in the mid-abdomen. Laboratory studies were remarkable for an elevated lactic acid level of 5.8 mmol/L (reference range, 0.7 to 2 mmol/L), which normalized after administration of 3 L of normal saline and 1 L of lactated Ringer's solution. A CT scan of the abdomen and pelvis demonstrated extensive atherosclerosis with resulting narrowing within the superior mesenteric artery (Figure 4, Figure 5) and wall thickening involving the distal small bowel with foci of gas within the liver due to portal venous gas. An arterial duplex scan showed greater than 70% stenoses of the superior mesenteric and celiac arteries. Stent placement by vascular surgery resulted in complete resolution of symptoms.

The diagnosis

The diagnosis is mesenteric ischemia due to atherosclerotic disease of superior mesenteric and celiac arteries. Most mesenteric ischemia cases are related to embolism or mesenteric arterial occlusive disease. Stenosis of the mesentery artery is common, occurring in up to 18% of the population over age 65 years; However, mesenteric ischemia is relatively rare, accounting for fewer than 1 in 1,000 hospital admissions for abdominal pain. Chronic mesenteric ischemia typically manifests as recurrent episodes of abdominal pain after eating, often referred as “intestinal angina.” It is classically dull, crampy, postprandial epigastric pain that occurs within the first hour after eating. Our patient did not have typical chronic symptoms. Symptoms can progress to acute mesenteric ischemia, which has a much higher associated morbidity and mortality.

CT angiography is the preferred initial diagnostic imaging modality, with sensitivities and specificities over 90%. Duplex ultrasonography of the mesenteric vessels is useful for the detection of high-grade celiac and superior mesenteric artery stenosis. Conventional arteriography is used when the results of noninvasive testing are equivocal and for therapeutic intervention. Revascularization is usually indicated in the presence of symptoms to prevent future bowel infarction. Options include percutaneous transluminal angioplasty with or without a stent and open surgical reconstruction. Restenosis can occur in up to 40% of patients who receive endovascular therapy and may require reintervention.

Pearls

  • Mesenteric ischemia should be considered in patients with acute or subacute abdominal pain and a history of atherosclerotic vascular disease.
  • CT angiography is the most accurate method of imaging to diagnose acute mesenteric ischemia; duplex ultrasonography is useful for the diagnosis of chronic mesenteric ischemia.

Case 4: Chronic Chagas cardiomyopathy

By Rooma Nankani, MD; Sindhu Naresh, MBBS; and Kosuke Yasukawa, MD, FACP

The patient

A 70-year-old woman visiting from Guatemala with a history of type 2 diabetes, stage 3 chronic kidney disease, and sick sinus syndrome (treated with a pacemaker six years previously) presented with progressive dyspnea on exertion of one-year duration and bilateral lower-extremity swelling. Physical examination was significant for decreased breath sounds over the right lower lung, jugular venous distention of 10 cm, and 2+ pitting edema in the bilateral lower extremities. Laboratory studies were unremarkable except for a creatinine level of 1.74 mg/dL (reference range, 0.60 to 1.10 mg/dL) and N-terminal pro B-type natriuretic peptide greater than 70,000 pg/mL (reference range, <353 pg/mL).

Figure 6 Chest X-ray showing a large right-sided pleural effusion with pulmonary venous congestion and cardiomegaly
Figure 6. Chest X-ray showing a large right-sided pleural effusion with pulmonary venous congestion and cardiomegaly.

A chest X-ray revealed a large right-sided pleural effusion with pulmonary venous congestion and cardiomegaly (Figure 6). An echocardiogram showed reduced right and left ventricular systolic function with an ejection fraction of 20% to 25% and dilatation of the right ventricle. Ischemic cardiomyopathy was unlikely given the lack of coronary calcifications on CT scan, and a technetium pyrophosphate scan did not suggest cardiac amyloidosis. Trypanosoma cruzi IgG antibody testing was positive, indicating chronic Chagas cardiomyopathy. The pleural effusion was consistent with transudate, and IV furosemide was started. The patient's symptoms improved, and she was discharged on a beta-blocker and a diuretic with plans for continued medical therapy and evaluation for implantable cardioverter-defibrillator placement. However, the patient was readmitted two weeks later for a right intertrochanteric fracture due to a fall. During anesthesia induction, she developed ventricular tachycardia and cardiac arrest. She was treated in the cardiac ICU for cardiogenic shock but died seven days later.

The diagnosis

The diagnosis is chronic Chagas cardiomyopathy. Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that can cause acute myopericarditis as well as chronic fibrosing myocarditis. Chagas disease is the most common cause of nonischemic cardiomyopathy in Latin America. It is estimated that there are 300,000 people with Chagas disease in the U.S. Cardiomyopathy develops in 20% to 40% of patients with the disease. Patients with chronic Chagas heart disease usually present with biventricular heart failure, although occasionally the first clinical manifestation is cardiac arrhythmia or cardioembolic stroke.

The diagnosis of chronic Chagas cardiomyopathy is based on the detection of T. cruzi antibodies. Polymerase chain reaction (PCR) is the most sensitive test in acute infection and can also be used for early detection of reactivation in an immunocompromised host. Endomyocardial biopsy is not generally required. Due to limited evidence, treatment for chronic Chagas cardiomyopathy is mostly extrapolated from other forms of heart failure. In patients with established cardiac disease, antitrypanosomal therapy is unlikely to change clinical outcomes; therefore, its routine use is not recommended.

Pearls

  • Chagas cardiomyopathy is an important cause of heart failure and arrhythmias in patients from areas where T. cruzi is endemic.
  • PCR is the most sensitive test for acute Chagas infection and can help with early detection of reactivation in immunocompromised hosts.

Case 5: Brachial plexus neuritis

By Silpa Kodali, MD; Sandeep Raparla, MD; and Kosuke Yasukawa, MD, FACP

The patient

Figure 7 An MRI of the brachial plexus showing asymmetric T2 hyperintensity along the right brachial plexus arrow
Figure 7. An MRI of the brachial plexus showing asymmetric T2 hyperintensity along the right brachial plexus (arrow).

A 70-year-old woman with a history of hypertension, asthma, and moderate spinal stenosis at L4-S1 presented with neck and right shoulder pain progressing to right-arm weakness and numbness for about two weeks. Physical examination revealed decreased strength of 3/5 in the right deltoid, biceps, and triceps as well as atrophy of the intraosseous muscles of the right hand. An MRI of the brain was unremarkable, and an MRI of the cervical spine showed no signs of nerve impingement or spinal stenosis. An MRI of the brachial plexus revealed T2 hyperintensity and atrophy of the right supraspinatus muscle, with asymmetric T2 hyperintensity along the right brachial plexus (Figure 7).

The patient had elevated inflammatory markers (CRP of 12 mg/L [reference range, 0.00 to 3.00 mg/L] and ESR of 48 mm/h [reference range, 0 to 22 mm/h]), and negative results on ANA, SSA/SSB, and an ANCA panel. Electromyography (EMG) showed diffuse right brachial plexopathy along with evidence of right median and ulnar nerve neuropathy. Transthyretin gene mutation was negative, indicating absence of transthyretin amyloidosis. Evaluation for plasma-cell dyscrasia was also negative with no evidence of monoclonal protein. The patient received prednisone, 20 mg for five days, and also underwent physical therapy with improvement of her right-arm weakness over two months.

The diagnosis

The diagnosis is brachial plexus neuritis, also called neuralgic amyotrophy or Parsonage-Turner syndrome. It is a rare syndrome that occurs more frequently in men and can affect any peripheral nerve, but most commonly the upper trunk of the brachial plexus is involved. Patients present with sudden onset of unilateral shoulder pain followed by progressive weakness, reflex changes, and sensory abnormalities, typically involving shoulder and proximal upper-limb musculature. In most cases, the cause is unknown. Possible triggers include viral infections, immunizations, surgery, strenuous exercise, and autoimmune diseases. Brachial plexus neuritis is a clinical diagnosis, but studies including EMG, nerve conduction, and MRI may support the diagnosis and exclude other pathologies. Characteristic MRI findings include diffuse high signal intensity on T2-weighted images involving one or more muscles innervated by the brachial plexus. No specific treatments have been evaluated in randomized controlled trials, but retrospective case series suggest that early corticosteroid therapy may reduce pain and hasten recovery in some patients.

Pearls

  • Brachial plexus neuritis should be considered in patients presenting with severe shoulder pain associated with motor and sensory symptoms; EMG and nerve conduction testing may help confirm the diagnosis and localize the lesions.
  • Characteristic features on MRI include diffuse high signal intensity on T2-weighted images involving one or more muscles innervated by the brachial plexus.

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