Epidemiology

• History: “Still’s disease” was first described in children in 1896 by the English physician, Sir George Frederic Still -> this entity should probably now be termed “Systemic Onset Juvenile Idiopathic Arthritis”
• Bimodal Age Distribution: however, cases have been reported in patients >70 y/o
  • Peak Between Age 15-25
  • Peak Between Age 36-46

---

Etiology

• Unknown
  • While viral pathogens (Rubella, Parvovirus B19), Mycoplasma Pneumoniae, and Yersinia Enterocolitica have been suspected to be etiologic, no definitive role for these pathogens has been proven

---

Diagnosis

• Anti-Nuclear Antibody (ANA): negative
  • Low titer positivity occurs in 10% of cases
• Rheumatoid Factor (RF): negative
  • Low titer positivity occurs in 10% of cases

---

Clinical-Yamaguchi Criteria

General Comments

• Sensitivity of Criteria: Yamaguchi criteria have the highest sensitivity of all of the published criteria
• Diagnostic Requirements: one of the following
  • 2 Major Criteria
  • 3 Minor Criteria

Major Criteria

• Fever: at least 39 degrees C and lasting at least 1 week
• Arthritis/Arthralgias: lasting at least 2 wks
• Salmon-Colored Non-Pruritic Macular/Maculopapular Rash: usually found over trunk or extremities during febrile episodes
• Leukocytosis (see Leukocytosis, [[Leukocytosis]]): at least 10k with at least 80% granulocytes

Minor Criteria

• Pharyngitis
• Lymphadenopathy
• Hepatomegaly or Splenomegaly
• Abnormal Liver Function Tests (LFT’s)
  • Elevated AST
  • Elevated ALT
  • Elevated LDH
• Negative ANA and RF

---

Clinical Manifestations

General Comments

• Must exclude conditions which might mimic adult-onset Still’s disease
  • Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) (Drug-Induced Hypersensitivity Syndrome, DIHS) (see Drug Rash with Eosinophilia and Systemic Symptoms, [[Drug Rash with Eosinophilia and Systemic Symptoms]])
  • Sepsis (see Sepsis, [[Sepsis]])

Cardiac Manifestations

• Myocarditis (see Myocarditis, [[Myocarditis]])
• Pericarditis (see Acute Pericarditis, [[Acute Pericarditis]])

Dermatologic Manifestations

• Evanescent Salmon-Colored Non-Pruritic Macular/Maculopapular Rash (see xxxx, [[xxx]])
  • Diagnosis: pathology is non-specific but demonstrates dermal edema and mild perivascular inflammation (lymphocytes, histiocytes) in superficial dermis
    • Immunofluorescence: slight deposition of C3 in vessel walls
    • Skin biopsy is important to rule out Sweet’s syndrome, vasculitis, and other disorders
  • Clinical
    • Predominantly involves trunk or extremities (but may involve face, palms of hands, soles of feet, or areas of tight clothing, such as under beltline or beneath the breasts)
    • Typically present during febrile episodes
    • Koebner Phenomenon: eruption can be invoked by stroking of the skin

Gastroenterologic Manifestations

• Abnormal Liver Function Tests (LFT’s)
  • Elevated AST
  • Elevated ALT
  • Elevated LDH
• Fulminant Hepatic Failure (see Fulminant Hepatic Failure, [[Fulminant Hepatic Failure]]): cases have been reported
• Hepatomegaly (see Hepatomegaly, [[Hepatomegaly]])

Hematologic Manifestations

• Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation, [[Disseminated Intravascular Coagulation]])
• Hyperferritinemia (see Hyperferritinemia, [[Hyperferritinemia]])
  • Decreased Percentage of Glycosylated Ferritin: percentage of ferritin which is glycosylated is lower than that in other rheumatologic diseases -> reported to be between 3.7-30%
    • Best to use in combination with serum ferritin
• Leukocytosis (see Leukocytosis, [[Leukocytosis]]): at least 10k with at least 80% granulocytes
• Lymphadenopathy (see Lymphadenopathy, [[Lymphadenopathy]])
• Microangiopathic Hemolytic Anemia (MAHA) (see Hemolytic Anemia, [[Hemolytic Anemia]])
• Pure Red Cell Aplasia (see xxxx, [[]])
• Reactive Hemophagocytic Syndrome (Macrophage Activation Syndrome) (see Hemophagocytic Syndrome, [[Hemophagocytic Syndrome]])
  • Diagnosis
    • Bone Marrow Biopsy: xxx
• Splenomegaly (see Splenomegaly, [[Splenomegaly]])
• Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (see xxxx, [[Thrombotic Thrombocytopenic Purpura]])

Pulmonary Manifestations

• Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])
• Interstitial Lung Disease: (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]]): has been reported
• Pharyngitis (see Pharyngitis, [[Pharyngitis]]): occurs in 69% of cases (and may recur with disease relapse)
• Pleural Effusions (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]]): neutrophil-predominant
• Pulmonary Infiltrates (see Pneumonia, [[Pneumonia]])

Rheumatologic Manifestations

• Arthralgias (see Arthralgias, [[Arthralgias]])
• Arthritis (see Arthritis, [[Arthritis]])
  • May evolve over months into a destructive polyarthritis
  • Fusion of wrist joints is characteristic (but seen in only a minority of cases): non-erosive narrowing of carpometacarpal and intercarpal joint spaces of the wrists is a classic finding
• Myalgias (see Myalgias, [[Myalgias]])

Other Manifestations

• Quotidian (Daily) or Double-Quotidian (Twice Daily) Fevers (see Fever, [[Fever]])
  • Temperature fluctuation may be dramatic: changes of 4 degrees can occur within 4 hrs
  • Fever may persist between spikes in 20-30% of cases

---

Clinical-Disease Patterns

• Monophasic Pattern (33% of cases): course lasts only weeks-months, completely resolving in <1 year
  • Predominant Clinical Findings: fever, rash, serositis, hepatosplenomegaly
• Intermittent Pattern (33% of cases): one or more disease flares with/without articular symptoms (remissions between episodes last weeks-1-2 years)
• Chronic Pattern (33% of cases): persistently active disease with predominant articular symptoms (and potentially destructive arthritis)

---

Treatment

Corticosteroids

• Corticosteroids (see Corticosteroids, [[Corticosteroids]])

Anti-TNF Therapy

• Adalimumab (Humira) (see Anti-TNF Therapy, [[Anti-TNF Therapy]])
• Etanercept (Enbrel) (see Anti-TNF Therapy, [[Anti-TNF Therapy]])
• Infliximab (Remicade) (see Anti-TNF Therapy, [[Anti-TNF Therapy]])

Other

• Anakinra (see Anakinra, [[Anakinra]])
• Hydroxychloroquine (see Hydroxychloroquine, [[Hydroxychloroquine]])
• Penicillamine (see Penicillamine, [[Penicillamine]])
• Azathioprine (Imuran) (see Azathioprine, [[Azathioprine]])
• Methotrexate (see Methotrexate, [[Methotrexate]])
• Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])
• Rituximab (Rituxan) (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]])

---

References

• Evaluation of serum ferritin as a marker for adult Still’s disease activity. Ann Rheum Dis. May 1992; 51(5): 683–685 [MEDLINE]
• Severe Systemic Inflammatory Response Syndrome With Shock and ARDS Resulting From Still’s Disease. Clinical Response With High-Dose Pulse Methylprednisolone Therapy. (CHEST 1999; 115:1738–1740)