A Patient with Pneumonia and Severe Arthralgias and other Findings. Is Failure to DIagnose Medical Malpractice?

Sometimes diseases are so rare and case presentations so atypical that it is difficult to blame a physician for failure to diagnose, and this should not lead to a medical malpractice action, no matter what the field: emergency medicine, primary care, or medical specialty care.  Here is a case in point:

A 61-year-old man presents to the emergency department (ED) with fever, dyspnea and a productive cough for 1 week that has failed to respond to outpatient antibiotics (levofloxacin). He also complains of worsening arthralgias in both lower extremities, particularly in his knees and ankles, as well as a 10-lb (4.54-kg) weight loss over the preceding 2 months. He is a former smoker with an 80-pack-year history, but there is no other significant medical history. He denies any recent travel, sick contacts, or occupational exposure to asbestos or mineral dust.  His only medications include over-the-counter analgesics for joint pains, and he denies having any drug allergies.

The physical examination reveals an elderly, cachectic male who appears to be in mild respiratory distress. His vital signs demonstrate an oral temperature of 101.4° F (38.6º C), pulse of 100 bpm, blood pressure of 110/70 mm Hg, respirations of 26 breaths/min, and an oxygen saturation of 93% on room air. Auscultation of the lungs demonstrates decreased breath sounds in the right lung base, with scattered fine rales. His heart sounds are regular and without any murmurs, rubs, or gallops. Abdominal examination does not reveal any tenderness or masses.  Clubbing of the fingers is noted; however, there is no evidence of pedal edema, joint swelling, erythema, or joint tenderness. No skin rashes are noted.

Laboratory tests are significant for a leukocyte count of 14.0 × 10³/µL (14.0 × 10⁹/L; normal range, 3.5-12.5 × 10³/µL); the remainder of the laboratory tests, including hematocrit, platelets, electrolytes, creatinine, and serum glucose, are within normal limits. A chest radiograph reveals a right lower-lobe (RLL) consolidation. The patient is started on intravenous (IV) ceftriaxone and azithromycin, and he is admitted with a diagnosis of community acquired pneumonia. Following admission, there is no improvement in his symptoms despite antibiotics, and blood cultures, sputum cultures, and Legionella serology tests return negative. A computed tomography (CT) scan of the chest is obtained, which reveals emphysema as well as mediastinal lymphadenopathy in the pretracheal and subcarinal areas (see Figure 1). A moderate right-sided pleural effusion along with multiple subcentimeter nodular opacities in the right middle and lower lobe are also noted, along with septal thickening (see Figure 2).

A rheumatology consultation is obtained for his lower-extremity arthralgias. There is no clinical evidence of synovitis or effusion in any of his joints, although there is evidence of mild arthritis of the knees, with suprapatellar enthesopathy seen on knee and ankle radiographs. He experiences no relief of his arthralgias with nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen. Opiates and gabapentin are added for pain relief. Additional laboratory tests are performed, which reveal an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Rheumatologic serology was negative, including rheumatoid factor, antinuclear antibody (ANA), and antineutrophil cytoplasmic antibodies (ANCAs), as well as normal serum complements. Based on the above evaluation, a presumptive diagnosis is made.

Based on the CT scan, the patient was suspected to have malignancy and an associated hypertrophic osteoarthropathy.  After obtaining the studies above, the patient underwent mediastinoscopy and lymph node biopsy, which resulted in the diagnosis of poorly differentiated non-small cell lung cancer (NSCLC).  Thoracentesis confirmed the malignant nature of the pleural fluid. Bone scintigraphy showed no metastatic disease, but it did demonstrate irregular uptake in both tibiae and fibulae, with evidence of arthritis in the major joints (see Figure 3); these findings are consistent with the final diagnosis of NSCLC-associated hypertrophic osteoarthropathy (HOA).

HOA syndrome is a condition characterized by proliferative periostitis of the long bones, especially in the distal and periarticular regions. It can result in proliferation of the synovial membranes, which causes painful and swollen joints; it is often accompanied by clubbing of the fingers.

This syndrome is classified into primary and secondary HOA. Primary is not associated with any other medical disorders; however, secondary (which is more common) is generally associated with lung cancer, TB, pulmonar abscess, bronchiectasis, emphysema, cystic fibrosis, interstitial lung disease, right-to-left cardiac shunts, and, other disorders.

While the etiology of HOA is still poorly understood, both neurogenic and humoral mechanisms may play a role. The frequent association of HOA with lung disease raises the possibility that circulatory bypass of the lungs may be responsible. One hypothesis regarding the etiology of HOA theorizes that megakaryocytes escape their normal fragmentation to platelets in the lung and reach the distal extremities, where they release growth factors.

Another hypothesis involves tumor production and the release of factors into the circulation (eg, vascular endothelial growth factor [VEGF]) that promote features of HOA, such as vascular proliferation, edema formation, and new bone formation.

When HOA is suspected, diagnostic tests should be directed at the chest because the most frequent cause of acute-onset HOA is a primary or secondary lung tumor. In one-third of patients with lung cancer clinical HOA predates the onset of respiratory symptoms, whereas in another third, patients present with respiratory symptoms simultaneously. In the remaining patients, signs and symptoms of HOA may appear after the diagnosis of malignancy is established.  Removal of lung tumors or the treatment of other causes of HOA results in regression of the clinical manifestations of HOA.  In mild-to-moderate cases, symptom control may be attempted with analgesics, such as nonsteroidal anti-inflammatory medications (NSAIDs), steroids, or narcotics; however, many patients find the associated pain to be disabling and their symptoms are often resistant to these treatments. A single dose of 4 mg of zoledronic acid has been effectively used to alleviate symptoms. In refractory cases, subcutaneous octreotide may be used to relieve symptoms.

Laboratory testing is not particularly useful in evaluating HOA; however, an elevated ESR of more than 50 mm/h and, in advanced cases, an elevated alkaline phosphatase level may be found.

Imaging studies are important in evaluating HOA. Radionuclide studies are more sensitive than radiography in the detection of the conditon. The appearance on radionuclide studies can range from an increased "bracelet-like" appearance to more diffuse, symmetrically increased uptake along the cortical margins of the diaphyses of the long, tubular bones (sometimes referred to as the "parallel tract" or "double stripe sign"). Although uncommon, there may be asymmetric and irregular involvement of the long bones (as seen in this case). Increased uptake in the distal phalanges is associated with marked clubbing. Although usually located in the peripheral skeleton, HOA can also affect the skull, clavicles, ribs, and scapulae. The disease is typically more active in the lower extremities than in the upper ones, and it is usually greater in the long bones distal to the knees and elbows than those proximal to these joints.

HOA has no prognostic significance and early detection may lead to the discovery of a potentially resectable lung carcinoma. Subclinical cases may be diagnosed by radiographs or by skeletal scintigraphy (which is more sensitive than plain radiographs), with an incidence of lung cancer of approximately 20%.

The patient in this case began chemotherapy treatment for his non–small cell lung cancer. The chemotherapy improved his arthralgias significantly. He was later discharged with outpatient oncology follow-up. After discharge, the patient did very well with high-dose NSAIDS and opiates, and he followed up with the oncologist for further treatment of his lung cancer.