A 29-year-old African American woman presents to her primary care physician complaining of ankle pain that she attributes to “arthritis” and a nonpruritic rash on her shins that both began approximately 6 days earlier. She has no history of arthritic complaints. Her temperature is normal and she has no chills, is not nauseated, and has not vomited. She has no abdominal or chest pain and is not short of breath. She has not noticed any change in skin color or in the color of her urine.
She works as an administrative secretary. She is not married but dates regularly. She is sexually active and says she practices “safe sex.” Her menstrual periods are regular and she has no vaginal discharge. She knows of no illnesses or similar symptoms among friends or family. She takes no medications, does not smoke cigarettes, and does not use illicit drugs. She drinks alcohol socially. She has not traveled outside the United States.
Physical examination reveals mild erythema, swelling, and tenderness in both ankles and red nodular lesions on the anterior tibial surfaces. Results of chest, abdominal, and pelvic examinations are normal.
What diagnostic clues do the history, physical examination, and labs offer, and which of the following tests would you order to help make a diagnosis?
A. Hepatitis serology
B. ASO titer
C. Rheumatoid factor serology
D. Culture for gonoccocus
E. Radiograph of the chest
Clues in the history. There are no helpful positive findings here, but the negative findings may be pertinent: No history of illness; no fevers, pulmonary or cardiac complaints, pruritus, or jaundice. She does not take medication or use illicit drugs; the latter might have been the source of a serum sickness–like reaction.
Physical clues. The only significant findings are the nodular rash on the lower legs and bilateral ankle arthritis. Pertinent for their absence are similar findings in any other joints.
Laboratory clues. There are none at this time.
Note: Sometimes it is useful to think of 2 apparently unrelated findings as part of a single process rather than related to separate pathologies.
Putting together the available facts, let’s consider the value of each of the laboratory studies:
A. Hepatitis serology. Hepatitis is common in this age group and is caused by various pathogens. Hepatitis A is rarely associated with arthritis or skin lesions. Hepatitis B is often associated with arthritis related to immune complexes with hepatitis antigen. Joint disease is often an early finding and predates jaundice and hepatomegaly. Related skin lesions manifest as urticaria or less commonly, petechiae. Hepatitis B is often transmitted by unprotected sex, IV drug use, tattoos, and other types of body fluid contamination. She has denied all of these risk factors. Hepatitis C, often transmitted by needle exposure, can present with arthritis caused by cryoglobulins. Patients with hepatitis C tend to have systemic symptoms, unlike our patient. Epstein Bar virus and cytomegalovirus can also cause hepatitis.
While it is not unreasonable to order hepatitis serology, the diagnosis is highly unlikely.
B. ASO titer. The tibial lesions described could be erythema nodosum (Figure), a finding that suggests streptococcal infection. Acute rheumatic fever may present with rash and without a sore throat, but missing here are characteristic fever and polyarthritis.
Overall, the level of suspicion is low for these or other streptococcal infections.
C. Rheumatoid factor. The patient fits the demographic for rheumatoid arthritis-female, young-but shows no signs or symptoms. Fatigue and fever, which typify the presentation, are absent. The disease process typically begins bilaterally in the hands at the PIP joints or in the wrist. Arthritis in both ankles as a presenting symptom, as seen here, would be highly unusual.
D.Culture for gonoccocus. She says that she practices safe sex, but . . . all the time? Negative findings on a pelvic examination don’t completely rule out gonorrhea. Ankle arthritis is a common sign but skin lesions typically appear on the hands and are more commonly pustular. A high index of suspicion warrants additional cultures of mucosa in the mouth and anus.
Gonorrhea is a possible diagnosis, but not likely in this patient.
E.Radiograph of the chest. This is the correct answer. The chest film revealed bilateral hilar lymphadenopathy with clear lung fields consistent with sarcoidosis. (See following discussion.)
The Diagnosis: Lofgren Syndrome
This patient offers a classic presentation of Lofgren syndrome (erythema nodosum, bilateral ankle arthritis, and bilateral hilar lymphadenopathy), which is virtually diagnostic of sarcoidosis. The patient’s age, race, and sex are all risk factors for this disorder. Mean age of onset for sarcoidosis is 35 years. This disease is seen more often in women than in men, and is also common in African Americans. The presence of 3 out of 4 clinical features (bilateral ankle arthritis, age younger than 40 years, erythema nodosum, and symptoms of fewer than 2 months’ duration) has 93% sensitivity, 99% specificity, and 75% positive predictive value for a diagnosis of sarcoidosis. Frequently, there are no other symptoms.
Sarcoidosis is occasionally diagnosed in asymptomatic people when after bilateral hilar lymphadenopathy is found on routine pre-employment chest films. Fortunately, most patients do well. The disease, however, can affect virtually any organ system. While the lungs are most commonly involved, there can be eye, brain, heart, liver, kidney, and metabolic abnormalities (eg, hypercalcemia) as well as skin and joint disease as seen in this patient.
• Isolated bilateral ankle arthritis is an unusual condition, usually related to circulating immune complexes.
• Erythema nodosum may be an isolated finding or associated with another condition (medications, infectious diseases, inflammatory diseases, or pregnancy).
• The combination of ankle arthritis and erythema nodosum is virtually diagnostic of sarcoidosis, and is called Lofgren syndrome.