The Seamstress With Sore Joints: Adult Onset Still

1
The Seamstress With Sore Joints Adult Onset
Stills Disease
Maureen Dubreuil MD, Eugene Kissin MD Department
of Internal Medicine, Boston Medical Center
Boston, Massachusetts 02118
Diagnosis Adult Onset Stills Disease (AOSD) is
an inflammatory disease of unclear etiology that
is diagnosed by the presence of five or more
clinical features, as presented by Yamaguchi and
colleagues.1
Different
ial Diagnosis
Epidemiology AOSD is a rare disease, with new
cases in 0.16 persons per 100,000 in a French
study.7 Gender distribution typically affects
women slightly more than men (60women),
particularly at older ages Age of onset
Median 25 years of age, with a bimodal peak and
15-25 years and 36-46 years of age.

• Case Presentation
• A 45-year-old Asian female presented in March
  2008 due to joint pain and swelling.
• Two months prior to presentation she developed
  pain in her wrists and ankles, worst at 2AM, and
  associated with swelling
• Pain improved slightly with naproxen, but this
  was stopped due to itching
• ROS Faint rash over arms and legs a few weeks
  prior, decreased appetite, episodic diaphoresis
  and chills
• PMH None significant
• SH Emigrated to US from Vietnam ten years
  ago. Work as a seamstress. Lives with husband
  and children in an urban area. No smoking,
  alcohol or drugs
• FH No known autoimmune disease
• Physical exam
• Vitals Temp , HR , BP , RR , sat , weight
  130 lbs

• Macrophage Activating Syndrome/
• Reactive Hemophagocytic
• Syndrome (MAS/RHS)
• MAS/RHS is a severe complication of AOSD due to
• dysregulation of macrophages in bone marrow and
• other reticuloendothelial tissues.12
• Diagnosis is made in a patient with active AOSD
  and
• Cytopenia of two cell lines
• Bone marrow biopsy showing hematophagocytosis by
  macrophages
• Clinical features fever, rash,
  hepatosplenomegaly and
• delerium
• Laboratory features cytopenias, coagulopathy and
  
• elevated ESR
• Triggers infections or medications

• Laboratory Studies

WBC PMNs 16,800/µl 90
Hematocrit MCV 32 88 FL
Platelets 464,000/µl
Serum chemistries Normal
BUN 3.9
Creatinine 0.8
ALT 28
AST 82
Alkaline Phos 75
Total bilirubin 0.5
Major AOSD Criteria (at least two) Major AOSD Criteria (at least two) Frequency () Frequency () Frequency () Frequency ()
Fever over 38C lasting one week or longer Typically quotidian or double-quotidian Fever over 38C lasting one week or longer Typically quotidian or double-quotidian 94-100 94-100 94-100 94-100
Joint pain lasting two weeks or longer Typically polyarticular Joint pain lasting two weeks or longer Typically polyarticular 68-100 68-100 68-100 68-100
Rash Typically salmon-colored and evanescent Rash Typically salmon-colored and evanescent 51-94 51-94 51-94 51-94
Abnormal white blood cell count Or other hematologic problems Abnormal white blood cell count Or other hematologic problems 62-93 62-93 62-93 62-93

Minor AOSD Criteria Minor AOSD Criteria Frequency () Frequency () Frequency () Frequency ()
Sore throat Sore throat 35-92 35-92 35-92 35-92
Lymphadenopathy or splenomegaly Lymphadenopathy or splenomegaly 15-81(J) 15-81(J) 15-81(J) 15-81(J)
Abnormal liver function tests or hepatomegaly Abnormal liver function tests or hepatomegaly 40-65 (J) 40-65 (J) 40-65 (J) 40-65 (J)
Absence of rheumatoid arthritis Absence of rheumatoid arthritis 93 93 93 93
Frequencies as reported by Effthimou et. al.2 Frequencies as reported by Effthimou et. al.2
Other clinical features Other clinical features Frequency () Frequency () Frequency () Frequency ()
Pleuritis Pleuritis 40 40 40 40
Pericarditis Pericarditis 30 30 30 30
Weight loss Weight loss 100 100 100 100
Dermatographism Dermatographism 92 92 92 92
Frequencies as reported by Singh et. al,3 except dermatographism, reported by Mehrpoor et. al.4 Frequencies as reported by Singh et. al,3 except dermatographism, reported by Mehrpoor et. al.4 Frequencies as reported by Singh et. al,3 except dermatographism, reported by Mehrpoor et. al.4 Frequencies as reported by Singh et. al,3 except dermatographism, reported by Mehrpoor et. al.4 Frequencies as reported by Singh et. al,3 except dermatographism, reported by Mehrpoor et. al.4
Common laboratory findings Common laboratory findings Frequency () Frequency () Frequency () Frequency ()
ESR elevated ESR elevated 99 99 99 99
Ferritin elevated Ferritin over 5 times normal value Glycosylated ferritin under 20 Ferritin elevated Ferritin over 5 times normal value Glycosylated ferritin under 20 67 40 78 67 40 78 67 40 78 67 40 78
WBC over 10,000/mm3 WBC over 10,000/mm3 92 92 92 92
WBC over 15,000/mm3 WBC over 15,000/mm3 88 88 88 88
Neutrophils over 80 percent Neutrophils over 80 percent 88 88 88 88
Anemia (Hgb less than10g/dL) Anemia (Hgb less than10g/dL) 68 68 68 68
Platelets over 400,000/mm3 Platelets over 400,000/mm3 62 62 62 62
Serum Albumin less than 3.5 g/dl Serum Albumin less than 3.5 g/dl 81 81 81 81
Elevated liver enzymes (any) Elevated liver enzymes (any) 73 73 73 73

Negative ANA Negative ANA 92 92 92 92
Negative RF Negative RF 93 93 93 93
Frequencies as reported by Effthimou et. al,2 except ferritin/glycosylated ferritin reported by Fautrel et. al.5 Frequencies as reported by Effthimou et. al,2 except ferritin/glycosylated ferritin reported by Fautrel et. al.5 Frequencies as reported by Effthimou et. al,2 except ferritin/glycosylated ferritin reported by Fautrel et. al.5 Frequencies as reported by Effthimou et. al,2 except ferritin/glycosylated ferritin reported by Fautrel et. al.5
Imaging Studies Imaging Studies
Xrays
Wrist Non-erosive narrowing of carpometacarpal and intercarpal joints with bony ankylosis Non-erosive narrowing of carpometacarpal and intercarpal joints with bony ankylosis Non-erosive narrowing of carpometacarpal and intercarpal joints with bony ankylosis Non-erosive narrowing of carpometacarpal and intercarpal joints with bony ankylosis Non-erosive narrowing of carpometacarpal and intercarpal joints with bony ankylosis
Ankles Tarsal ankylosis, same characteristics as wrist Tarsal ankylosis, same characteristics as wrist Tarsal ankylosis, same characteristics as wrist Tarsal ankylosis, same characteristics as wrist Tarsal ankylosis, same characteristics as wrist
Findings reported by Medsger et. al.6 Findings reported by Medsger et. al.6 Findings reported by Medsger et. al.6
ESR CRP ANA 58 mm/hr 35 Negative
Rheumatoid factor Negative
Anti-CCP SSA/SSB RPR Negative Negative Negative

Ferritin 37,469 ng/mL

• Pathophysiology
• The etiology remains unknown, and is thought to
  be due to
• an environmental trigger, such as an infection,
  in combin-
• ation with a genetic susceptibility. Proposed
  triggers include
• viruses and bacterial infections. The pathway
  leading to
• clinical disease has yet to be fully elucidated,
  but is thought
• to involved altered cytokine production.
• Altered Cytokine Production
• IL-1 is produced by activated macrophages, and is
  
• involved in the TH1 (cell-mediated) immune
  response.
• IL-1 levels are elevated in some patients with
  AOSD,8 and are markedly reduced in patients who
  improved when treated with an IL-1ß receptor
  antagonist .
• IL-18 is a member of the IL-1 cytokine family and
  is also elevated in patients with AOSD levels
  correlate with liver dysfunction and elevated
  ferritin.9,10
• IL-6 is produced by macrophages and lymphocytes,
  and induces acute phase reactants.
• IL-6 levels are elevated in serum of AOSD
  patients.14

Hepatitis B/C serologies Negative
Gonorrhea PCR Negative
Chlamydia PCR Negative

• Treatment
• Treatment of AOSD remains largely empiric as
  there have
• not been large trials due to the rarity of the
  disease.
• NSAIDs are first line therapy, but approximately
  80 of patients require additional treatment.
• Ibuprofen 800 mg orally four times daily
• Naproxen 500 mg orally twice daily
• Glucocorticoids
• Prednisone 0.5 to 1.0 mg/kg daily
• Disease-modifying antirheumatic drugs (DMARDs)
  Typically used in patients with episodic or
  chronic disease course to prevent complications
  from arthritis, or as glucocorticoid-sparing
  agents.
• Methotrexate
• Cyclosporine
• Chloroquine/hydroxychloroquine
• Cyclophosphamide
• Biologics are used in approximately 15 of
  patients who do not respond to other therapy.
  TNF inhibitors have been successful in some
  cases, but IL-1ß and IL-6 antagonists show the
  most promising results.

SAMPLE
A B
Figure 1. (A) Wrist X-rays of a patient with AOSD
showing non-erosive narrowing of the
carpometacarpal and intercarpal joints with bony
ankylosis. (B) Cervical spine X-ray showing facet
joint narrowing and ankylosis. Radiographs
courtesy of Dr. Burton Sack.
Figure 3. Frequency of AOSD patients with
self-limited, episodic and chronic disease
course, as reported by Pouchot et. al.11

• References
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• Efthimiou P, Paik PK, Bielory L. Diagnosis and
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• Mehrpoor G, Owlia MB, Soleimani H, Ayatollahi J.
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• Fautrel B, Le Moël G, Saint-Marcoux B, Taupin P,
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• Medsger TA Jr, Christy WC. Carpal arthritis with
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Infectious Non-Infectious
Gonococcal arthritis Reactive arthritis
Meningococcemia Rheumatologic
Parvovirus SLE
EBV Rheumatoid arthritis
Disseminated lyme disease Seronegative arthritis
Primary HIV
Hepatitis B
Figure 1. Evanescent, salmon-pink maculopapular
rash over the leg of a woman with Adult Onset
Stills Disease. The rash typically affects
the proximal limbs and trunk, but spares the face
and distal limbs, and is often associated or more
pronounced with fever. Photograph by E. Kissin
Figure 2. Serum ferritin (ng/ml) level over time.
Arrow indicates initiation of treatment with
prednisone.