SEARCH

SEARCH BY CITATION

Keywords:

  • cellulitis;
  • erythema sarcoidosis;
  • Löfgren's syndrome;
  • nodosum;
  • polyarthritis

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. Author contributions
  7. Competing interests
  8. References

Löfgren's syndrome is an acute-onset presentation of sarcoidosis that can be easily missed in an ED setting. A case is reported of Löfgren's syndrome presenting as erythema nodosum with bilateral ankle oedema. Although rare, this diagnosis should be considered when examining a patient with erythema nodosum and articular symptoms.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. Author contributions
  7. Competing interests
  8. References

Sarcoidosis is a non-caseating granulomatous disorder of unknown aetiology. It has a female predominance, with the prevalence ranging from <1 to 64 per 100 000.1 Given its multi-systemic nature, it can involve the lungs, eyes, liver, heart, skin and lymph nodes. Up to 40% of sarcoidosis presents acutely, often with systemic symptoms such as fever, fatigue, nausea and vomiting.2

Löfgren's syndrome is one such acute-onset presentation, and is characterized by the clinical complex of erythema nodosum, bilateral hilar lymphadenopathy and acute polyarthritis, usually at the ankles, knees, wrists or elbows. It is more common among Scandinavian, Irish and Puerto Rican women.3 The disease is usually self-limiting, with a generally good prognosis.

Case report

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. Author contributions
  7. Competing interests
  8. References

A 25-year-old otherwise fit and healthy white man presented with a 5 week history of an elliptical area of persistently erythematous swelling in the right pre-tibial region after minor trauma against a piece of wooden furniture. He had concomitant symptoms of persistent back, bilateral calf and ankle pain and bilateral pitting oedema.

He had just returned aboard a long-haul flight from travelling abroad in the UK and Portugal. While overseas, he was not involved in any water sports or activities, bushwalking or spelunking. He was seen by a local doctor overseas and treated for presumed cellulitis with oral antibiotics (500 mg Flucloxacillin four times daily) for 10 days. However, his condition progressively worsened and of he developed nausea, vomiting and headache, along with a low-grade fever of 37.7°C.

On presentation, the patient was afebrile, and haemodynamically stable. He appeared pale but comfortable. There was a single elliptical erythematous macular area measuring 5 × 15 cm on the dorsal aspect of the right shin, but the left leg was normal. There was bilateral calf and ankle tenderness and pitting oedema, along with slightly limited range of movement in both ankles, but with no neurovascular compromise. The examination was otherwise unremarkable with no shortness of breath, neck stiffness or rash.

Blood tests revealed mild leukocytosis with 12.20 × 109 cells/L, with 8.49 × 109 neutrophils. Inflammatory markers were raised, with CRP of 26 and ESR of 38. Blood and urine cultures were negative. A right leg tibia/fibula X-ray and ultrasound scan showed no signs of abscess formation or osteomyelitis. A diagnosis of deep venous thrombosis was considered, although his solitary risk factor of long-haul travel and the negative examination findings made this unlikely.

He was started on intravenous Ceftriaxone (1 g i.v. twice daily), fluids and analgesia, and admitted to the short stay unit for observation for management of suspected cellulitis. His clinical picture improved a little and he was subsequently discharged home for further investigation and treatment for a presumptive atypical inflammatory process under the Hospital in the Home unit.

However, the patient failed to improve over the next few days, with continued pain, oedema and erythema of the legs. The patient was afebrile and had no other systemic symptoms. Further laboratory tests were conducted, with anti-CCP and ANA negative. The patient's medication was changed to Cephazolin i.v. 2 g twice daily. On day 8 of antibiotic treatment, the patient developed three new erythematous nodular lesions on his right calf and shin, consistent with erythema nodosum. Antibiotics were then ceased.

For further evaluation of systemic causes of his illness, a chest X-ray was ordered to exclude lymphoma and sarcoidosis. It revealed bilateral hilar lymphadenopathy suggestive of sarcoidosis. This was confirmed with a CT scan of his chest and abdomen with widespread nodularity throughout the lung, especially on the left fissure (Figs 1,2). The liver and spleen were unremarkable.

image

Figure 1. CT scan showing bilateral hilar lymphadenopathy.

Download figure to PowerPoint

image

Figure 2. CT scan showing widespread lung nodules seen in sarcoidosis.

Download figure to PowerPoint

In light of the findings, the patient was referred to the Rheumatology Clinic and managed conservatively for Löfgren's syndrome. He was started on 50 mg Diclofenac three times daily orally. He was to be followed up by a rheumatologist in 1 month.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. Author contributions
  7. Competing interests
  8. References

Löfgren's syndrome, first described by Löfgren in 1952,4 comprises of the clinical triad of erythema nodosum, polyarthritis and bilateral hilar lymphadenopathy. Given its multi-systemic nature and unspecific manifestations, clinical presentations of this acute-onset form of sarcoidosis can be missed and mistaken for cellulitis or other rheumatic conditions, especially in an ED setting. This is further complicated by the existence of variants, where some patients present with bilateral hilar lymphadenopathy and periarticular inflammation of the ankles without erythema nodosum.5

There is evidence to show that Löfgren's syndrome is associated with human leukocyte antigens (HLAs) B8, A1 B8, DR3 and DR17; an association with HLA-DRB1*03 in particularly has a positive effect on the prognosis.6 Hizawa et al. have also shown that polymorphism of the CCR2 gene might relate to the varying prevalence of sarcoidosis and Löfgren's syndrome among people of differing ethnicities.7

Traditionally, a biopsy is needed for definitive diagnosis of Löfgren's syndrome; however, several studies have shown this may be achieved via a combination of clinical and radiological diagnosis with no less specificity. A review of 186 patients with Löfgren's syndrome showed that in classical cases of the disease, routine biopsy is not needed for confirmation, but is warranted where findings are atypical for sarcoidosis.5 Raised serum angiotensin-converting enzyme level, a negative tuberculin skin test, a CT scan showing hilar lymphadenopathy and a gallium-67 scan with increased uptake are adjunct tools to support the diagnosis.

As part of the workup for erythema nodosum, it is important to rule out other causes such as infective agents (histoplasmosis, coccidioidomycosis, Group A beta-haemolytic streptococci, tuberculosis), drug reactions, inflammatory bowel disease and malignancy.

The treatment for Löfgren's syndrome is primarily conservative, with NSAIDs and bed rest recommended.8 Some patients also require corticosteroids as second-line therapy. Patients with Löfgren's syndrome generally have a good prognosis, especially those who present with erythema nodosum.9 The disease is usually self-limiting, becoming inactive within the first year.

Author contributions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. Author contributions
  7. Competing interests
  8. References

DC was the principal author of the case report. AM was the supervisory author and clinician overseeing the care of this patient.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. Author contributions
  7. Competing interests
  8. References
  • 1
    Bauer HJ, Löfgren S. International study of pulmonary sarcoidosis in mass chest radiography. Acta Med. Scand. 1964; 425: 1039.
  • 2
    Fauci AS et al. Harrison's Principles of Internal Medicine, pgs 17ed. New York: McGraw Hill, 2008.
  • 3
    Siltzbach LE, James DG, Neville E et al. Course and prognosis of sarcoidosis around the world. Am. J. Med. 1974; 57: 84752.
  • 4
    Löfgren S, Lundback H. The bilateral hilar lymphoma syndrome: a study of the relation to age and sex in 212 cases. Acta Med. Scand. 1952; 142: 25964.
  • 5
    Mana J, Gomez-Vaquero C, Montero A et al. Löfgren's syndrome revisited: a study of 186 patients. Am. J. Med. 1999; 107: 2405.
  • 6
    Gruenwald J, Eklund A. Löfgren's Syndrome: Human Leukocyte Antigen Strongly influences the disease course. Am. J. Respir. Crit. Care Med. 2009; 179: 30712.
  • 7
    Hizawa N, Yamaguchi E, Furuya K, Jinushi E, Ito A, Kawakami Y. The role of the C-C chemokine receptor 2 gene polymorphism V64I (CCR2-64I) in sarcoidosis in a Japanese population. Am. J. Respir. Crit. Care Med. 1999; 159: 65962.
  • 8
    Ohta H. Acute-onset sarcoidosis with erythema nodosum and polyarthralgia (Löfgren's syndrome) in Japan: a case report and a review of the literature. Int. Med. 2006; 45:1452.
  • 9
    Mana J, Salazar A, Pujol R, Manresa F. Are the pulmonary function test and the markers of activity helpful to establish the prognosis of sarcoidosis? Respiration 1996; 63: 298303.