January 31, 2020
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A Löfty diagnosis amid shades of sarcoidosis

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Adam J. Brown, MD
Adam J. Brown

The “black sheep” in a family of already unusual diseases, Löfgren syndrome presents acutely unlike the subtle onset and gradual disease progression characteristic of other types of sarcoidosis. Although often defined by a unique triad of symptoms, Löfgren syndrome still relies on a diagnosis of exclusion, and is often mistaken for other rheumatologic and infectious conditions.

If there is one thing that Healio Rheuminations podcast host Adam J. Brown, MD, associate staff physician in the department of rheumatic and immunologic diseases at Cleveland Clinic, wants to accomplish, it is helping clinicians understand Löfgren syndrome and other members of the sarcoidosis family.

In a recent episode, Brown introduced the topic by reviewing the case of a 57-year-old woman with subacute inflammatory arthritis and a “mild erythematous patch on her forearm,” whose blood test was negative for antinuclear antibody (ANA) and cyclic citrullinated peptide (CCP). “Overall, she was doing well,” he said.

Brown ultimately diagnosed the patient with Löfgren syndrome based on the aforementioned triad: erythema nodosum, bilateral hilar lymphadenopathy (BHL), and polyarthralgia.

However, there was one other key element that confirmed Brown’s suspicions. “It is considered an acute attack of sarcoidosis, but it behaves very differently from other sarcoidosis, because it is almost always self-limiting,” he said.

Brown suggested that the self-limiting nature of the condition makes it a unique prospect for rheumatologists to manage. “How often in rheumatology are we able to tell a patient, ‘Don’t worry about it, it is probably going to go away’?” he said. “Most of the time, our diseases are here to stay.”

Swedish Power Duo

Swedish clinician Sven Halvar Löfgren first described the condition in the 1946 paper with fellow Swedish clinician Holger Lundbeck after reviewing 178 cases of erythema nodosum in which 57% of the cohort had painful joints and 27% had joint swelling.

“Initially, they thought it was tuberculosis, or a few were caused by streptococcus,” Brown said. “They later found out that it was sarcoidosis. Most of the patients also had inflammatory arthritis.”

Building off the desire to differentiate the disease from tuberculosis, in a 1951 paper, Löfgren and Lundbeck reported on 212 patients with BHL and negative tuberculin skin tests. The results showed that 113 of these patients had erythema nodosum, 101 had joint pain, and 70 had joint swelling, according to Brown.

“Löfgren noted, presciently, that the articular symptoms were mild, and usually subsided within a couple of weeks,” Brown said. “He pretty much described Löfgren syndrome, with the triad, and noted that most of these symptoms would go away. [However,] he called it ‘bilateral lymphoma syndrome’ — he didn’t put his name to it apparently.”

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A Specific Population

Another intriguing factor regarding Löfgren syndrome is its prevalence in Scandinavia and Spain. “It is interesting [that Löfgren and Lundbeck] had 212 patients at one hospital,” Brown said. “Clearly, there is something about this particular population that was predisposed to this kind of sarcoidosis.”

In the present day, Brown noted that much of the data on this syndrome comes from Spain, with one study claiming that Löfgren syndrome represents nearly half of sarcoidosis cases in the country.

Brown highlighted a group in Barcelona that followed 113 patients prospectively between 1974 and 1996. “This is a long time of collecting patients,” he said, noting that they were followed for a mean of 58 months.

The Barcelona group expanded understanding of the disease. They defined Löfgren syndrome as erythema nodosum, periarticular ankle inflammation plus bilateral hilar adenopathy. “The periarticular ankle inflammation is very important,” Brown said. “Most patients retain a range of motion of the ankle, which argues against major synovitis.”

Results of the Barcelona study also showed that arthralgias occurred in other joints besides the ankles in about two-thirds of patients. “Also of note, uveitis was present in a few patients,” Brown added.

Only 6% of the patients from Barcelona had an episode of recurrence between 2 and 20 years. “This is a significantly low recurrence rate,” Brown said. “No other patient developed an alternative diagnosis if they had this triad.”

If there is another factor that researchers studying this disease have learned over time, it is that it is marked by seasonal variability, according to Brown. “The majority of cases happen between March and July,” he said. “Nearly 70% of cases happen within these months. This looks toward some sort of environmental factors that possibly trigger this disease.” – by Rob Volansky

References:
Healio Rheuminations podcast: https://www.healio.com/rheumatology/podcasts/rheuminations/episode-eight

For more information:
Adam J. Brown, MD, can be reached at 9500 Euclid Avenue, Cleveland, OH 44195; email: BROWNA22@ccf.org.

Disclosure: Brown reports no relevant financial disclosures.