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Löfgren's syndrome is a subtype of acute sarcoidosis involving:
It is named after Swedish researcher, Sven Löfgren (1910-1978), who worked on sarcoidosis in the 1940s and 1950s.
Patients with Löfgren's syndrome generally have a good prognosis, are unlikely to develop chronic disease (sarcoidosis is considered chronic when symptoms last for more than three years) and most patients with Löfgren's can expect a self-limiting illness and spontaneous remission. As with other forms of sarcoidosis, aetiology is unknown - the interaction of an unidentified environmental trigger and a genetically susceptible host is likely. 'A case-control etiologic study of sarcoidosis' (ACCESS) - a large US-based case-control study - failed to find any single environmental or occupational causative factor. What differentiates individuals who develop Löfgren's syndrome from other forms of sarcoidosis is also unclear: the effects of different polymorphisms in the the CR2 gene on chromosome 3 are being investigated, one particular haplotype of which appears to be associated with an increased risk of Löfgren's syndrome.
Incidence varies widely around the world, with some populations (notably the Irish and Nordic people) more prone to developing Löfgren's syndrome. A study in Catalonia suggested an incidence of 0.65 per 100,000 per annum. It is much rarer in other areas of the world, such as Japan.
- Strong female predominance (85%).
- Young to middle-age (mean age of onset - 35 years).
- Seasonality - presentation is more common in spring months (northern hemisphere).
- Cough or dyspnoea
- Fever or malaise
- Erythema nodosum.
- Periarticular ankle inflammation/bilateral ankle arthritis.
- Bilateral Achilles tendonitis (rare).
Presentation appears to differ between men and women, with a predominance of erythema nodosum amongst women and bilateral ankle arthritis in men.
Löfgren's syndrome needs to be distinguished from other causes of:
- Erythema nodosum, eg infection (Streptococcus spp., tuberculosis, mycoplasma), drugs, inflammatory bowel disease, non-Hodgkin's lymphoma, Behçets disease.
- Hilar lymphadenopathy - lymphoma, tuberculosis and lung cancer need to be excluded, particularly where lymphadenopathy is not symmetrical.
- Pyrexia of unknown origin.
Investigations indicating active sarcoidosis include:
- CXR (abnormalities include mediastinal lymphadenopathy or pulmonary infiltration).
- Gallium-67 scan (may be used when CXR is normal; shows increased hilar or paratracheal uptake).
- Lung function tests (decreased forced vital capacity).
- Serum calcium level (may be elevated).
- Serum angiotensin-converting enzyme (may be increased).
- Lymph node biopsy.
The ankle arthritis may best be demonstrated by MRI scan.
- Once Löfgren's syndrome can be confidently diagnosed, the patient can be reassured that the condition is benign and normally self-limiting.
- Routine biopsy is not required to confirm the diagnosis unless there are atypical features.
- Management is supportive, eg non-steroidal anti-inflammatory drugs for arthralgia.
- Follow-up should continue until any hilar lymphadenopathy has resolved.
Prognosis is usually very good, typically resolving within 6 months to 2 years. In a minority, disease remains active (8%) or relapses (6%), sometimes after a long period. Good prognostic markers include:
- Normal serum angiotensin-converting enzyme levels at diagnosis.
- Particular human leukocyte antigen (HLA) types - being HLA-DRB1*03 negative increases the risk of non-resolving disease.
Further reading & references
- Judson MA; The management of sarcoidosis by the primary care physician. Am J Med. 2007 May;120(5):403-7.
- Turchin I, Nguyen K, Menard HA; Cough, fever, joint pain and tender nodules: what is your call? CMAJ. 2008 Jan 15;178(2):151-2.
- Sven Halvar Löfgren; Sven Halvar Löfgren, whonamedit.com
- Lofgren S; Primary pulmonary sarcoidosis. I. Early signs and symptoms. Acta Med Scand. 1953;145(6):424-31.
- Newman LS, Rose CS, Bresnitz EA, et al; A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med. 2004 Dec 15;170(12):1324-30. Epub 2004 Sep 3.
- Rossman MD, Kreider ME; Lesson learned from ACCESS (A Case Controlled Etiologic Study of Sarcoidosis). Proc Am Thorac Soc. 2007 Aug 15;4(5):453-6.
- Spagnolo P, Renzoni EA, Wells AU, et al; C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome. Am J Respir Crit Care Med. 2003 Nov 15;168(10):1162-6. Epub 2003 Jul 25.
- Valentonyte R, Hampe J, Croucher PJ, et al; Study of C-C chemokine receptor 2 alleles in sarcoidosis, with emphasis on family-based analysis. Am J Respir Crit Care Med. 2005 May 15;171(10):1136-41. Epub 2005 Mar 4.
- Fite E, Alsina JM, Mana J, et al; Epidemiology of sarcoidosis in Catalonia: 1979-1989. Sarcoidosis Vasc Diffuse Lung Dis. 1996 Sep;13(2):153-8.
- Ohta H, Tazawa R, Nakamura A, et al; Acute-onset sarcoidosis with erythema nodosum and polyarthralgia (Lofgren's syndrome) in Japan: a case report and a review of the literature. Intern Med. 2006;45(9):659-62. Epub 2006 Jun 1.
- Mana J, Gomez-Vaquero C, Montero A, et al; Lofgren's syndrome revisited: a study of 186 patients. Am J Med. 1999 Sep;107(3):240-5.
- Sipahi Demirkok S, Basaranoglu M, Dervis E, et al; Analysis of 87 patients with Lofgren's syndrome and the pattern of seasonality of subacute sarcoidosis. Respirology. 2006 Jul;11(4):456-61.
- Mana J, Gomez-Vaquero C, Salazar A, et al; Periarticular ankle sarcoidosis: a variant of Lofgren's syndrome. J Rheumatol. 1996 May;23(5):874-7.
- Ortiz V, Holgado S, Olive A, et al; Achilles tendinitis as the presentation form of Lofgren's syndrome. Clin Rheumatol. 2000;19(2):169-70.
- Grunewald J, Eklund A; Sex-specific manifestations of Lofgren's syndrome. Am J Respir Crit Care Med. 2007 Jan 1;175(1):40-4. Epub 2006 Oct 5.
- Anandacoomarasamy A, Peduto A, Howe G, et al; Magnetic resonance imaging in Lofgren's syndrome: demonstration of periarthritis. Clin Rheumatol. 2007 Apr;26(4):572-5. Epub 2006 Aug 2.
- Grunewald J, Eklund A; Lofgren's syndrome: human leukocyte antigen strongly influences the disease Am J Respir Crit Care Med. 2009 Feb 15;179(4):307-12. Epub 2008 Nov 7.
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Dr Chloe Borton
Dr Chloe Borton