Published: 3 December 2020

Publications

A bitter-Sweet syndrome with potential autoimmune connections

Published: 3 December 2020
Prescriber Update 41(4): 79

December 2020

Background

A 51-year-old woman developed fever, arthralgia and a general painful macular rash a few days after influenza vaccination. The case was reported to the Centre for Adverse Reactions Monitoring (CARM ID 137192). A skin biopsy confirmed a diagnosis of Sweet syndrome. The case report also stated the patient had presumed Sjögren’s syndrome.

This article describes Sweet syndrome and how it may be connected to Sjögren’s syndrome.

Sweet syndrome

Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare skin condition, characterised by fever and sudden onset of painful skin lesions that appear mostly on the limbs and neck.^1,2 Mucosal surfaces such as the eyes and mouth may also be involved.²

Sweet syndrome belongs to a heterogenic group of neutrophilic dermatoses³, with neutrophils accumulating in the dermis or in the fatty layer of tissue just below the skin.³ It was first described by Dr Robert Douglas Sweet in 1964.²

The cause of Sweet syndrome is often unknown. However, there are three subtypes based on aetiology: classical or idiopathic, malignancy-associated, and drug-induced.⁴

• Classical or idiopathic Sweet syndrome: the disorder occurs by itself for no known reason. Some people experience an upper respiratory infection, gastrointestinal infection, or influenza-like illness that precedes their skin lesions by one to three weeks.³
• Malignancy-associated Sweet syndrome: associated with certain types of cancer, such as leukaemia.³
• Drug-induced Sweet syndrome: including granulocyte-colony stimulating factor (G-CSF), azathioprine, All-trans retinoic acid (ATRA) and, with less evidence, vaccination, anticancer agents, trimethoprim + sulphamethoxazole and other antibiotics, nonsteroidal anti-inflammatory medicines and hydroxychloroquine.^5,6

Sweet syndrome is usually treated with corticosteroids. The treatment usually results in rapid improvement of symptoms, but lower doses may be required for several weeks to months to prevent reoccurrence of symptoms.²

Sjögren’s syndrome

Sjögren’s syndrome is an autoimmune condition that may develop either as a primary disease or as a secondary complication of another autoimmune disease, such as rheumatoid arthritis or lupus. It most commonly affects older women. The main symptoms are dry mouth and eyes but other parts of the body, such as joints and kidneys, may also be affected.⁷

Treatment is primarily symptomatic. Artificial tears are used for dry eyes, and dry mouth may be relieved by saliva substitutes or medicines that stimulate saliva flow such as pilocarpine. All patients must receive regular dental care to prevent cavities and tooth loss.⁷ Hydroxychloroquine is also used for treatment of Sjögren’s syndrome.

Is Sweet syndrome associated with vaccination or Sjögren’s syndrome?

The patient in the CARM case report developed Sweet syndrome after influenza vaccination. A few cases of Sweet syndrome after vaccination have been described in the literature.⁵ One woman developed Sweet syndrome 12 hours after influenza vaccination.⁸

The patient in the case reported to CARM had also previously been diagnosed with Sjögren’s syndrome. Sweet syndrome has been associated with a multitude of conditions, including Sjögren’s syndrome, but the evidence for an association has been very weak^5,6. A literature review including articles up to October 2019 only found six publications where Sweet syndrome had occurred in patients with secondary Sjögren’s syndrome, and one publication where a patient with primary Sjögren’s syndrome developed Sweet syndrome.⁶

Four cases of Sweet syndrome have been reported to CARM. The case mentioned above is the only one that reports both Sweet and Sjögren’s syndromes. Six other cases have been reported where Sjögren’s syndrome is listed as either a reaction or a possible pre-existing condition. Data is very limited in all of these CARM reports.

References

1. Mayo Clinic. 2020. Sweet’s syndrome. URL: mayoclinic.org/diseases-conditions/sweets-syndrome/symptoms-causes/syc-20351117 (accessed 28 September 2020).
2. Oakley A. 2015. Acute febrile neutrophilic dermatosis. In: DermNet NZ September 2015. URL: dermnetnz.org/topics/acute-febrile-neutrophilic-dermatosis/ (accessed 28 September 2020).
3. NORD National Organization for Rare Disorders. 2015. Sweet syndrome. URL: rarediseases.org/rare-diseases/sweet-syndrome/ (accessed 28 September 2020).
4. Merola JF. 2020. Sweet syndrome (acute febrile neutrophilic dermatosis): pathogenesis, clinical manifestations, and diagnosis. In: UpToDate 9 April 2020. URL: uptodate.com/contents/sweet-syndrome-acute-febrile-neutrophilic-dermatosis-pathogenesis-clinical-manifestations-and-diagnosis (accessed 9 October 2020).
5. Heath MS, Ortega-Loayza AG. Insights into the pathogenesis of Sweet's syndrome. Frontiers in Immunology 10: 414. DOI: 10.3389/fimmu.2019.00414 (accessed 20 October 2020).
6. Manzo C, Pollio N, Natale M. 2019. Sweet's syndrome following therapy with hydroxychloroquine in a patient affected with elderly-onset primary Sjogren's syndrome. Medicines 6(4): 111. DOI: 10.3390/medicines6040111 (accessed 28 September 2020).
7. American College of Rheumatology. 2019. Sjögren's syndrome. URL: rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Sjogrens-Syndrome (accessed 28 September 2020).
8. Jovanović M, Poljacki M, Vujanović L. 2005. Acute febrile neutrophilic dermatosis (Sweet's syndrome) after influenza vaccination. Journal of the American Academy of Dermatology 52(2): 367–9. DOI: 10.1016/j.jaad.2004.07.061 (accessed 20 October 2020).