Transcript adult onset still disease 1

Dr. Müge Bıçakçıgil Kalaycı
ADULT ONSET STILL DISEASE
 Multi-system inflammatory disease
 begins with a sore throat

may develop days to weeks before
 the typical quotidian fever
 Rash
 Joint pains
ETIOLOGY
 no etiologic factor has been identified
 Infectious??
 prodromal sore throat
 fever
 Possible mechanism;
- viral agent initiates a cascade of the immunological
events resulting in the characteristic clinical syndrome
of AOSD.
 Implicated organisms in AOSD
-Rubella
-Mycoplasma
-Ebstein Barr
-Borelia burgdoferi
-Staphylococcus
-Cytomegalovirus
-Parvovirus
-Mumps
-Yersinia enterocolitica
-Parainfluenza
Brucela abortus
Clinical Features
Common Clinical Features
*Fever of at least 39ºC lasting one week or longer
*Arthralgias or arthritis lasting two weeks or longer
*Characteristic rash which is a macular or
maculopapular, nonpruritic, salmon-pink
eruption usually apparent over the trunk or
extremities during febrile episodes
* Leukocytosis (10,000/µL or greater) with 80
percent or more granulocytes
* Sore throat
* Recent development of significant lymph node swelling
* Hepatomegaly or splenomegaly
*Abnormal liver function studies, particularly
aminotransferases and lactate dehydrogenase
*Negative tests for antinuclear antibody and rheumatoid
factor
FEVER
 Quotidian or "double-quotidian" with a brief peak
in the late afternoon or early evening.
 Temperature swings can be dramatic, with changes
of 4ºC occurring in four hours.
 Approximately 20 percent of cases, fever persists
between spikes.
 Over 99 % of patients manifest with fever > 39 0 C
FEVER
 The febrile paroxysms are cyclic and tend to recur every 24 or
sometimes every 12 hours. Characteristically very high in the
evening, returning to normal by morning.
 Paroxysms are heralded by shaking chills, followed by 2-4
hours of high fever (> 104°F), and ending with defervescence
and drenching sweats
RASH
 Still's rash is seen in 86% of patients
 Periodic appearance and location
 Appears during febrile attacks and may last for several
hours
 It is typically salmon-colored (infrequently
erythematous), maculopapular and may be confluent
or show areas of central clearing.
 Trunk, neck, extremity( extensor surface)
RASH
 Usually the face, palms, and soles are spared.
 Dermatographism: is an exaggerated cutaneous
urticarial response to cutaneous stimuli (ie, the
scratch test).
 Rash is typically nonpruritic.
Articular Manifestations

Arthralgias dominate the early clinical picture
 During the first 6 mos. the onset of polyarthritis is
expected in > 90% of patients and may involve large and
small articulations
 Myalgias
 Affected joints: the knees, wrists, ankle, elbow, shoulder,
PlPs, DlPs, TMJ and cervical spine.
 Bony ankylosis of carpal, carpometacarpal. Intertarsal
joints
 Erosive and destructive polyarthritis, especially in those
with a chronic polyarticular course
Reticuloendothelial Disease
 Splenomegaly

Very common early in the disease and reflects tissue infiltration with inflammatory
cells and heightened immunologic activity within the reticuloendothelial system (RES).
 Palpable or radiographic demonstration of splenomegaly is seen in 42% of individuals
 Hepatomegly
 40% of patients are found to have hepatomegaly
 70% demonstrate abnormalities of hepatic enzymes at some time during their illness
Lymphadenopathy
 65% of AOSD patients.
 Generalized mild to moderate nodal enlargement of
nontender lymph nodes located in the cervical, axillary,
epitrochlear, or inguinal regions.
 Mesenteric, para-aortic and hilar nodes may be discovered
during diagnostic imaging
 SEROSITIS

 Pleuritis (40%)
 Pleural effusions are usually bilateral, seldom large enough
to be symptomatic, and rarely produce pleural thickening.
 Thoracentesis often yields bloody, exudative effusions with
white blood cell counts ranging from 3-20 x 103/mm3 with a
polymorphonuclear predominance.
 Pneumonitis
 Pneumonitis is found in over 20% of patients
 These individuals often appear septic with complaints of
fever, dry cough, dyspnea and are found to have pulmonary
infiltrates that are unresponsive to anti-infective therapy
 Infiltrates tend to be bilateral more commonly than
unilateral, alveolar or interstitial in pattern and responds
well to anti-inflammatory therapy with steroids
Laboratory
Investigations
Absence of antinuclear antibodies
Elevated serum amyloid A
Absence of rheumatoid factor,
Thrombocytosis
Elevated ESR and C-reactive protein
Elevated serum ferritin and
glycosylated ferritin
Neutrophilic leukocytosis
Elevations the hepatic enzymes
Hypoalbuminemia
 Leukocytosis
 Leukocytes counts generally range between 12,500-40,000 cells/mm3,
with the highest recorded to be 69,000
 ESR
 90% of AOSD patients have an ESR > 50 mm/hr and 50% have and
ESR > 90 mm/hr.

Hyperferritinemia

It has been suggested that extreme elevations of the
acute phase reactant, ferritin, may be of diagnostic value
in assessing patients with AOSD

Hyperferritinemia with values between 4000 30,000
mg/ml have often been reported in association with the
onset and/or flare of disease activity

Levels as high as 250,000 mg/ml have been reported
AOSD.
Diagnosis

Diagnosis

Still disease lacks serologic test or histopathology and
thus, remains a clinical
diagnosis of exclusion.

AOSD is now being considered earlier in the course of
evaluation of patients with fever, dermatitis and
arthritis.

Diagnostic steps should include a comprehensive,
noninvasive workup, documentation of fever pattern
 Yamaguchi et al 1992
 AOSD Total of > 5 criteria (including 2 major)
 Major Criteria
Fever > 39°C
Arthralgia > 2 wks.
Still's rash
Neutrophilic leukocytosis
Minor Criteria
Sore throat
LN or splenomegaly
Liver dysfunction
Negative RF & ANA
 specificities greater than 92%, the sensitivity of Yamaguchi
(96%)
Treatment
Treatment

NSAIDS or Aspirin
 Mild disease with no life- threatening visceral involvement
 20-25 % respond (good prognosis group with mild disease
activity)
 Aspirin or an NSAID should be continued for one to three
months following disease remission.
 GLUCOCORTICOSTEROIDS
 Patients with very high fever,
 Joint involvement that is disabling
 Potentially life-threatening visceral involvement
(myocarditis)
 Starting dose of 0.5 to 1.0 mg/kg per day PO
 Immunomodulating drugs
 There are no controlled trials assessing the efficacy of any
of the immunomodulating drugs in ASD
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* Intramuscular gold salts
* Hydroxychloroquine,
* Azathioprine,
* Cyclophosphamide,
* Cyclosporine,
* Sulfasalazine,
* Methotraxate
* Intravenous immune globulin,
* Anti-TNF-alpha agents