A Japanese patient with Löfgren's syndrome with an HLA-DR12 allele and review of literature on Japanese patients.

Sarcoidosis is a granulomatous disorder of unknown etiology, with several clinical manifestations. Löfgren's syndrome is an acute type of sarcoidosis, characterized by the triad of arthritis, erythema nodosum, and bilateral hilar lymphadenopathy (BHL), which spontaneously resolve within about 2 years. Löfgren's syndrome is common among young white women from Nordic countries and Ireland, but it is very rare in Japan. Because the incidence of Löfgren's syndrome varies according to race, most studies on Löfgren's syndrome, including HLA typing, have been reported in Western countries. Indeed, HLA-DR3 has been reported to be associated with Löfgren's syndrome in Western countries, although the association between HLA typing and Japanese Löfgren's syndrome remains unclear. Here we present a Japanese patient with Löfgren's syndrome. A 34-year-old female patient was hospitalized with arthritis and erythema nodosum. Chest computed tomography revealed mediastinal and BHL. Endobronchial ultrasound-guided transbronchial needle aspiration showed non-caseating epithelioid cell granulomas. Löfgren's syndrome was thus diagnosed. Her ankle arthralgia and bilateral ankle swelling recovered without steroid treatment within two months, and the BHL almost completely diminished one year after admission. Her HLA genotype contains DR12. We also reviewed the literature on 11 Japanese patients with Löfgren's syndrome, showing that HLA-DR12 is present in five out of nine patients (55.6%). The relevant data were unavailable in the remaining three patients. Importantly, only 5.4% of registered donors in the Japan Marrow Donor Program are positive for this allele. We suggest the potential link between HLA-DR12 and the pathogenesis of Löfgren's syndrome in Japanese patients.

Variation in the lymphotoxin-alpha/tumor necrosis factor locus modifies risk of erythema nodosum in sarcoidosis.

Sarcoidosis is a multi-system inflammatory disease with organ involvement that varies by race and sex. Family studies indicate that genes play a role in the etiology and extent of organ involvement in sarcoidosis. In this study, we evaluated whether 25 variants distributed in 19 genes with a known role in inflammation were associated with erythema nodosum status in 659 sarcoidosis patients and 658 controls from A Case-Control Etiologic Study of Sarcoidosis (ACCESS). We found no association with affectation status; however, a variant in the promoter of tumor necrosis factor (TNF) at position -308 was found to be associated with erythema nodosum in Caucasian sarcoidosis patients (study-wide P=0.027). When separated by sex, a variant in intron 1 of lymphotoxin-alpha (LTA), a gene adjacent to TNF, was associated with erythema nodosum in female Caucasian sarcoidosis patients (study-wide P=0.027). These DNA variants frequently occur together in Caucasians, and each variant has individually been associated with erythema nodosum in sarcoidosis patients. These results confirm that variation in the LTA/TNF gene cluster modifies a major skin manifestation of sarcoidosis and may explain the higher rate of erythema nodosum in females with sarcoidosis.

Acute-onset sarcoidosis with erythema nodosum and polyarthralgia (Löfgren's syndrome) in Japan: a case report and a review of the literature.

Löfgren's syndrome is an acute form of sarcoidosis that is characterized by erythema nodosum (EN), bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. This syndrome is common among white people, but is considered rare among Japanese people. We present the case of a 26-year-old Japanese woman with Löfgren's syndrome. The patient complained of polyarthritis and EN of the lower extremities that lasted for 3 months. A chest radiograph revealed BHL and nodular shadows. The angiotensin-converting enzyme (ACE) level was within the normal range. Transbronchial lung biopsy revealed a noncaseating granuloma with giant cells. Six Japanese cases of Löfgren's syndrome have been reported previously. Five of the seven Japanese patients with Löfgren's syndrome had normal ACE levels; all of them exhibited BHL. Löfgren's syndrome should be considered as a possibility when examining a patient with EN and articular symptoms, even if the patient is Japanese.

67Gallium scans in Löfgren's syndrome.

Comparison of 67Gallium scans of head and neck showed no significant difference in intensity of uptake between patients with Löfgren's syndrome and sarcoidosis patients with similar chest x rays having other modes of onset. Uptake was the same in the 12 white and 18 black patients studied. Thus, the increased bronchoaveolar lavage lymphocytosis which has been shown to be a feature of Löfgren's syndrome is not paralleled by gallium uptake. Gallium scores had no predictive value regarding outcome showing no significant difference between 13 patients who recovered within a year and 15 patients who developed chronic disease. The outcome was more favorable in white patients and in those whose onset was with Löfgren's syndrome.

Erythema nodosum in the Negev area--a survey of 50 patients.

Fifty patients in the Negev area with erythema nodosum (EN) were studied retrospectively. The clinical picture and demographic characteristics did not differ markedly from those in the literature. In contrast to most European studies but like those from Egypt, we found streptococcal pharyngitis to be the major cause of EN. Conspicuously, sarcoidosis is a rare cause of EN in the Negev. The low incidence of EN in the Negev--2 cases/100,000 people per year--as opposed to Europe--14 cases/100,000 people per year--is hardly explained by the low occurrence of sarcoidosis in Israel. Other factors, unknown at present, may account for this low incidence.