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Used with permission. Url
http://www.hopkins-arthritis.org/case/case11/11_case.html
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by
Lisa Christopher-Stine, M.D.
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Summary of Prior Events |
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October, 1998: The 22 year old (18 years at this time) patient
experienced her first episode of severe pain and swelling of both knees of 4
days duration. The pain resolved with ibuprofen.
November, 1998:
She experienced pain and swelling of both knees, which resolved
spontaneously.
January,
1999: Her left wrist became erythematous and swollen, and she was
eventually bedridden due to right knee swelling not relieved with ibuprofen.
Four days later, she reported to a local emergency room complaining of daily
spiking fevers (as high as 102.6 in the evening) and chills. Upon further
questioning, she reported a 30-pound unintentional weight loss over the
prior 3 months. She was admitted to the community hospital. Her right knee
was aspirated and broad- spectrum antibiotics are instituted.
She was
prescribed a short course of oral steroids with no clear diagnosis and was
lost to follow-up.
January,
2002: She returned to the local emergency room with complaints of wrist
and knee pain and daily fevers for the past week. She was given antibiotics
and aspirin and discharged. Three weeks later, she returned to the hospital
and was admitted with arthralgias, fever, myalgias, pharyngitis, and
pre-syncope.
She was given the diagnosis of acute rheumatic fever. Prednsione, 5 mg
daily and roficoxib were prescribed and she was discharged.
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History of Present Illness |
February, 2002: She was admitted to an outside hospital with chest pain,
bilateral wrist and knee pain. She was placed on ampilcillin/sulbactam. An
echocardiogram revealed pericarditis which required a pericardial window due
to a sizable pericardial effusion. Shortly thereafter, bilateral pleural
effusions developed, and bilateral chest tubes were placed.
SHE WAS TRANSFERRED TO JOHNS HOPKINS HOSPITAL FOR FURTHER WORKUP AND
DIAGNOSIS.
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Presentation to Johns Hopkins Rheumatology Clinic |
- Past Medical History: Right wrist fracture
- Family History: Raised by foster parents; biologic parents’
health history unknown
- Social History: Nonsmoker, no alcohol or intravenous drug use;
one sexual partner; not currently employed
- Allergies: Naprosyn, which caused hives
- Medications at transfer: Ampicillin/sulbactam, azithromycin,
celecoxib, prednisone, 60 mg daily
- Review of Systems: No alopecia, Raynaud’s phenomenon, sicca,
photosensitivity, or apthous ulcers
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Physical Examination |
- Temperature: 36.7 C; BP: 117/65; RR 16
- General: Young African American woman alert and oriented
- Skin: No lymphadenopathy or subcutaneous nodules; no rash
- HEENT: No alopecia, no oral ulcers, no pharyngeal erythema
- Chest: Breast examination normal; Lungs dull to percussion at
left base
- Heart: Regular with no pericardial friction rub or murmur
- Abdomen: no hepatosplenomegaly
- Extremities: No clubbing, no Raynaud’s phenomenon, 2+ pulses
- Musculoskeletal: Minimal boutonniere deformities (see photo);
No active synovitis; normal range of motion of all joints both actively
and passively
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Laboratory Findings |
- WBC — 24.1 with a PMN predominance of 92%
- Hematocrit — 30.2
- Platelets — 808
- Urinalysis — negative for protein or red cells
- ALT — 77
- AST — 100
- Alkaline phosphatase — 116
- Albumin — 2.7
- Haptoglobin — 492
- ASO — 198 (normal is 0-115 IU/ml)
- Hand radiographs — normal
- Echo — Mitral valve prolapse with no regurgitation; no pericardial
effusion
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Differential Diagnosis |
- [ ] Acute Rheumatic Fever
- [ ] Systemic Lupus Erythematosus
- [ ] Rheumatoid Arthritis
- [ ] Adult Onset Still’s Disease
- [ ] Malignancy with paraneoplastic process
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Clinical Course |
The
patient was given the provisional diagnosis of Adult Onset Still’s
Disease. She was prescribed low dose prednisone and celecoxib upon
discharge from the hospital. Over the next several months, however, she
developed progressive pain and swelling of the wrists and ankles requiring
methotrexate therapy. Her WBC count decreased, and her hematocrit improved
slightly with iron supplementation. Her ASO titers have remained within
normal limits, and her rheumatoid factor and ANA remain negative. An
extensive search for the etiology of her microcytic anemia has been
unrevealing. Over the past year, she has developed considerable hand and
wrist deformities (See radiographs below) despite methotrexate
therapy and oral corticosteroids. She has never had a recurrence of
serositis and has not developed any additional systemic symptoms, including
fevers. She began etanercept two months ago, along with low dose prednisone
and has experienced considerable relief of her symptoms.
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Right
Wrist:
Diffuse radiocarpal and carpal-metacarpal joint space narrowing is
evident with questionably small bony erosion involving the ulnar styloid.
There are also some small erosions in the distal carpal and
carpal-metacarpal joints. Subtle fusion is not excluded. |
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Left
Wrist:
Some erosive changes involving the bones suspected involving the distal
carpal and metacarpal joint with joint space narrowing diffusely
throughout. Possibility of some fusion involving the mid-carpal joints
is not excluded. |
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Discussion |
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Although systemic lupus erythematosus seemed plausible in light of the
arthritis and serositis, the negative ANA and lack of other diagnostic
features made this diagnosis very unlikely. Although a solid tumor
malignancy, such as breast cancer, can present with pleural and/or
pericardial effusions and articular symptoms, the patient’s young age and
lack of confirmatory cytology on the pleural fluid essentially ruled out
this diagnosis. Although rheumatoid arthritis can present with pleural
effusions, this is typically a later finding, and the effusion typically has
a very low glucose, which was not seen in this patient. The presence of
pharyngitis, along with the presence of fever and arthralgia, also helps to
narrow the differential diagnosis, as sore throat is distinctly uncommon in
most rheumatic diseases presenting with arthralgias and constitutional
symptoms with or without a rash. Pharyngitis, however, is commonly
associated with Acute Rheumatic Fever and Adult Onset Still’s Disease and
these diagnoses remain primary considerations in the differential diagnosis.
The distinction between these two diseases can be nebulous, as illustrated
by this case. The two diseases have a number of similarities (see table
below).
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Adult Onset Still’s Disease
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Acute Rheumatic Fever
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Pericarditis |
Yes
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Yes
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| Fever >39oC |
Yes
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Yes
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| Arthralgia |
Yes
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Yes
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| Arthritis |
Yes
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Yes
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| Rash |
Yes
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Yes (E.
Marginatum)
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| Pharyngitis |
Yes
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Yes
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| Pleuritis |
Yes
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Rare
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| Weight Loss |
Yes
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Rare
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Lymphadenopathy |
Yes
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Rare
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Acute rheumatic
fever occurs two to four weeks after group A beta-hemolytic streptococcal
infection of the pharynx. It is thought to be related to a series of
immunologic reactions to antigenic components of the streptococcus which
also cross reacts with various human tissues. The clinical features include
fever, migratory arthralgias, destructive inflammatory lesions of the
myocardium, pericardium, endocardium, valvular structures, periarticular
regions, lungs, and subcutaneous tissues. The associated chorea may be
transient or persistent. There has been a rapid decline of cases since the
1950’s , presumed to be due to better overall hygiene and widespread
antibiotic use in children. The average incidence in affluent countries is
less than 5 per 100,000. The diagnosis of Acute Rheumatic Fever is
substantiated by the Jones Criteria (below).
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JONES
CRITERIA*
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MAJOR
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MINOR
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- Carditis
- Polyarthritis
- Chorea
- Erythema marginatum
- Subcutaneous nodules
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- Prolonged P-R interval
- Arthralgia
- Fever
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Supporting Evidence:
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Laboratory Findings
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- Positive Throat Culture
- Rising ASO Titer
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- Elevated ESR
- Elevated CRP
- Elevated Acute Phase Reactants
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*JAMA
268:2069-2073, 1992. |
Acute rheumatic
fever is usually managed by treating the underlying streptococcal infection
with penicillin. The associated arthritis is sensitive to high dose
salicylates (4-8 g/day); other non-steroidal anti inflammatory drugs may
also be used. A prompt response to salicylates supports the diagnosis.
Steroids are reserved for refractory arthritis and severe carditis.
Prophylactic penicillin is recommended, but the cumulative dose needed
remains controversial.
Adult Onset
Still’s Disease (AOSD) is an acute febrile illness in young adults. It
usually affects multiple organs, but is a diagnosis of exclusion. The
etiology of ASD is unknown; however, a number of infectious triggers have
been suggested, including viruses and bacterial pathogens including
Mycoplasma pneumoniae. Clinical features include a high fever, arthralgia
and arthritis, phayngitis, typical rash (evanescent salmon-colored, macular
or maculopapular eruption), lymphadenopathy, and serositis. Chronic
arthritis and constitutional symptoms are common. Several diagnostic
criteria sets for AOSD have been proposed. Two of these sets of criteria are
shown in below.
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TWO SETS
OF DIAGNOSTIC CRITERIA FOR AOSD
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Cush, et al.(ref)
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Yamaguchi,
et al.(ref)
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Requires ALL
of the following:
- Fever > 39 degrees
- Arthralgia or arthritis
- Rheumatoid factor
< 1:80
- ANA < 1:100
In addition to ANY TWO of the following:
- WBC count > 15,000
- Still’s rash
- Pleuritis or Pericarditis
- Hepatomegaly, Splenomegaly, or Lymphadenopathy
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Presence of
5 or more criteria, of which at least 2 are Major — yields 96%
sensitivity; 92% specificity
Major Criteria
- Fever > 39 degrees > 1 week
- Arthralgia/arthritis > 2 weeks
- Typical rash
- WBC > 10 K with 80% PMN's
Minor Criteria
- Sore throat
- Lymphadenopathy
- Increased LFT's
- RF and ANA negative
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The triad of
fever, rash, and arthralgia are often absent during the first month of the
illness. A quotidian (daily, spiking) or “double-quotidian” fever curve is a
hallmark of the disease. The rash is usually truncal or present on the
proximal extremities precipitated by mechanical or thermal stimulation. It
is most apparent during fever periods. The usual joints affected are wrists,
knees, and ankles in descending order. Two thirds of cases experience
polyarticular arthritis and one third have monoarticular symptoms.
Approximately 1/3 of patients have chronic persistent disease with
progressive joint damage. Half of all AOSD patients require some medication
10 years after their illness. The management of AOSD remains empirical, and
there are few controlled studies to date. Most patients require steroids,
and many need high doses for six months followed by chronic maintenance
therapy. There is some evidence that methotrexate is effective, and newer
studies demonstrate efficacy with the TNF-alpha inhibitor, etanercept.
This case
illustrates a difficult diagnostic dilemma. The high ASO titer probably
represents an acute phase reactant. The lower than expected ferritin level
is most likely a manifestation of the patient’s underlying anemia. Some
suggest that serum ferritin values above 3000 ng/mL in a patient with
typical symptoms, in the absence of infection, should lead one to consider
the diagnosis of AOSD. Although very elevated ferritin levels are associated
with AOSD, lower levels do not rule out the disease and are not part of the
diagnostic criteria. The long-term management of this illness is evolving
but appears to respond to cytokine-targeted therapies.
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References |
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Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and
Kawasaki Disease of the Council on Cardiovascular Disease in the Young,
American Heart Association. JAMA 268:2069-2073, 1992.
Stollerman GH,
Markowitz M, Taranta A, et al. Jones criteria (revised) for guidance in the
diagnosis of rheumatic fever. Circulation 32:664-668, 1965.
Jones TD.
Jones criteria (revised) for guidance in the diagnosis of rheumatic fever.
JAMA 126:481, 1944.
Yamaguchi
M, Ohta A, Tsunematsu T, et al. Preliminary criteria for classification of
adult Still's disease. J Rheumatol 19:424, 1992.
Cush JJ,
Medsger TA, Jr, Christy WC, et al. Adult-onset Still's disease: Clinical
course and outcome. Arthritis Rheum 30:186, 1987.
Nguyen K,
Weisman M. Severe throat as a presenting symptom of adult onset Still’s
disease: a case series and review of the literature. J Rheumatol
24:592-7, 1997.
Masson C,
le Loet X, Liote F, et al. Adult Still’s Disease. Part 1. Manifestations and
Complications in sixty-five cases in France. Rev Rheum (Engl Ed)
11:748-57, 1995.
Ohta A,
Yamaguchi M, Tsunematsu T, et al. Adult Still's disease: A multicenter
survey of Japanese patients. J Rheumatol 17:1058, 1990.
Fautrel
B, Borget C, Rozenberg S, et al. Corticosteroid sparing effect of low dose
methotrexate treatment in adult Still's disease. J Rheumatol 26:373,
1999.
Kraus A,
Alarcon-Segovia D. Fever in adult onset Still's disease. response to
methotrexate. J Rheumatol 18:918, 1991.
Fujii T,
Akizuki M, Kameda H, et al. Methotrexate treatment in patients with adult
onset Still's disease retrospective study of 13 Japanese cases. Ann Rheum
Dis 56:144, 1997.
Husni ME,
Maier AL, Mease PJ, et al. Etanercept in the treatment of adult patients
with Still's disease. Arthritis Rheum 46:1171, 2002.
Kelly J,
Chowienczyk J, Gibson T. Sore throat and hyperferritenaemia. R Soc
Med 94:400-401, 2001.
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