Adult onset still diseaseM06.1

Special form of primary chronic polyarthritis in adults, an autoinflammatory syndrome with recurrent, urticarial exanthema, lymphadenopathy, re- and intermittent fever attacks > 39 °C, carditis, liver and spleen enlargement, pericarditis, rarely myocarditis. See also Still's syndrome in childhood.

• Main criteria (n. Yamaguchi et al.):
  • Integument: Volatile, urticarial, morbilliform or scarlatiniform exanthema on extremities, trunk and face with high tendency to recur. Intensification often in the evening, often not present in the morning (90%)
  • Intermittent fever attacks > 39 °C with 1-2 peaks/day, persisting for at least 1 week (> 95%)
  • Arthralgias for at least 2 weeks
  • Arthritides > 2 weeks (90%)
  • Leukocytosis (> 10,000/μl) with at least 80% neutrophils.
• Secondary criteria:
  • Sore throat
  • Visceral manifestations: Generalized, non-painful lymphadenopathy with or without splenomegaly (45%)
  • Transaminases and/or LDH elevated
  • Pericarditis (25%)
  • Pleuritis (25%)
  • Rheumatoid factor negative
  • ANA negative

The diagnosis "adult-onset Still's syndrome (AOSD)" requires at least 5 criteria, including 2 main criteria.

The skin symptoms in detail: AOSD is associated with skin involvement in 80% of patients, which can be divided into two subgroups: a typical and an atypical rash. A total of 86% of patients present with the typical transient and salmon-colored macular or maculopapular rash on the trunk and/or proximal limbs, rarely also on the head, palms or soles. It usually develops in the late afternoon during febrile episodes and disappears without scarring and is usually associated with mild itching or burning (Cozzi A et al. 2016). In contrast, 78% of patients present with an atypical rash. Both typical and atypical skin symptoms can occur simultaneously (Lee JY et al. 2012). Atypical rash encompasses a broad spectrum of different lesions. The most common atypical skin manifestation is characterized by extensive, itchy, scaly and reddened papules, some of which coalesce into erythematous plaques on the head, trunk and extensor sides of the limbs. The skin lesions may also be erythematous urticarial, brown flat lichenoid in linear distribution, possibly as a Köbner phenomenon, and dermatomyositis-like with heliotropic plaques on the eyelids. More rarely, acneiform skin manifestations include vesiculopustular lesions, extensive plaques and angioedema (Cozzi A et al. 2016; Lee et al. 2012).

Nonspecific signs of inflammation with leukocytosis and neutrophilia, BSG and CRP significantly elevated, often high ferritin level, thrombocytosis possible (Höllweger N et al. 2018).

Dermal edema with dilated blood and lymph vessels, sparse perivascular infiltrate of neutrophil granulocytes, lymphocytes and macrophages.

NSAIDs, glucocorticoids and targeted therapies are available for treatment. NSAID monotherapy results in disease control in only 7-15% of patients; therefore, patients usually require additional treatment with corticosteroids (Franchini et al. 2010). Targeted therapy is required in a third of patients whose disease is inadequately controlled with NSAID and/or glucocorticoid treatment, with interleukin-1 inhibitors being the drugs of choice (anakinra, canakinumab). The interleukin-6 antagonist tocilizumab can be used as an alternative treatment approach, while TNF-α inhibitors are only considered third-line agents and have shown less promising results in studies (Feist E et al. 2018).

The adult breastfeeding syndrome is counted among the extended circle of autoinflammatory syndromes.

In rare cases, overlaps are described with Kikuchi-Fujimoto Syndrome, a cervically emphasized self-limited lymphadenopathy.

1. Cozzi A et al. (2016) Cutaneous manifestations of adult-onset Still's disease: a case report and review of literature. Clin Rheumatol 35: 1377-1382.
2. Feist E et.al (2018) Mechanisms, biomarkers and targets for adult-onset Still's disease. Nat Rev Rheumatol14: 603-618
3. Franchini S (2010) Efficacy of traditional and biologic agents in different clinical phenotypes of adult-onset Still's disease. Arthritis Rheum 62: 2530-2535
4. Herzer P (1986) Still syndrome in adults. Dtsch Med Wochenschr 111: 865-867
5. Höllweger N et al (2018) Adult onset Still`s syndrome. J Dtsch Dermatol 16: 491-492
6. Kaufmann S et al (1981) Still syndrome in adults. A contribution to the differential diagnosis of "fever of unknown origin". Med World 32: 1692-1697
7. Lee JY et al. (2005) Histopathology of persistent papules and plaques in adult-onset Still's disease. J Am Acad Dermatol 52: 1003-1008.
8. Lee JY et al. (2012 Evanescent and persistent pruritic eruptions of adult-onset Still's disease: a clinical and pathologic study of 36 patients.Semin Arthritis Rheum 42: 317-326
9. Lee JY et al. (2012) Evanescent and persistent pruritic eruptions of adult-onset still disease: a clinical and pathologic study of 36 patients.Semin Arthritis Rheum 42: 317-326
10. Prendiville JS et al. (2004) A Pruritic Linear Urticarial Rash, Fever, and Systemic Inflammatory Disease in Five Adolescents: Adult-Onset Still Disease or Systemic Juvenile Idiopathic Arthritis sine Arthritis? Pediatr Dermatol 21: 580-588
11. Zollner RC et al. (1997) Hyperferritinemia in Still syndrome in the adult and reactive hemophagocytic syndrome. Med Klin (Munich) 92: 494-498