66 - Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Adult-Onset Still Disease, and Rheumatic Fever Flashcards
Most common dermatologic finding in RA
Rheumatoid nodule
Usual location of rheumatoid nodules
Pressure points such as the olecranon, extensor surfaces of the forearms, and the Achilles tendon
Development of rheumatoid nodules in patients without chronic synovitis or radiographic findings, and mild or no systemic manifestations
Involves men predominantly, and many develop frank RA
Rheumatoid nodulosis
In children, similar lesions of rheumatoid nodulosis are termed
Most regress within 2 years; progression to RA is extremely rare
Pseudorheumatoid nodulosis
Distribution of pseudorheumatoid nodulosis
Tibia
Dorsal foot
Scalp
Low-dose methotrexate, often used for the treatment of RA, may precipitate erythema in and enlargement of preexisitng rheumatoid nodules, known as
Accelerated nodulosis
A papular reaction to _____ has been reported as a syndrome of clustered, erythematous, indurated papules arising most commonly on the proximal extremities and buttocks
Methotrexate
Another possible cutaneous complication of ______ therapy (occasionally other immunosuppressive drugs) in RA is development of Epstein-Barr virus-associated multifocal cutaneous lymphoproliferative disease
Methotrexate
Reactive granulomatous dermatitis has been proposed as an inclusive term for the following 3 syndromes
Interstitial granulomatous dermatitis
Palisaded neutrophilic and granulomatous dermatitis
Interstitial granulomatous drug reaction
Presents as symmetric skin-colored to erythematous smooth, umbilicated, or crusted papules, primarily on the elbows and extremities
Histologically, early features include intense neutrophilic inflammation, karyorrhectic debris, and leukocytoclastic vasculitis. Later findings are piece-meal areas of collagen degeneration and palisades of histiocytes and small granulomas, eventually accompanied by areas of fibrosis
Palisaded neutrophilic and granulomatous dermatitis
Tumor necrosis factor inhibitors and allopurinol have been implicated as causes
Palisaded neutrophilic and granulomatous dermatitis
Usually asymptomatic, this presents symmetrically on the lateral upper trunk and proximal inner arms and thighs, and occasionally on the buttocks, abdomen, breast, and umbilicus
Histopathologic findings include a dense, diffuse infiltrate of histiocytes arranged in a band-like configuration in middle or deep reticular dermis
Epidermis with basal vacuolization is rarely seen
Interstitial granulomatous dermatitis
Probably often used interchangeably with IGD
Present as erythematous to violaceous plaques, often annular, concentrated on inner arms, proximal medial thighs, proximal trunk, and intertriginous sites
Histologic findings are similar to IGD, but should include interface dermatitis with basal vacuolar degeneration, areas of dyskeratosis, and prominent tissue eosinophilia
Interstitial granulomatous drug reaction
Commonly implicated drugs in IGDR
Calcium channel blockers
Beta-blockers
Lipid lowering agents
Angiotensin-converting enzyme inhibitors
Very rare cutaneous manifestation in patients with severe RA
Lesions are usually chronic, erythematous, and urticaria-like plaques and papules that are sharply marginated
Histopathologically, lesions have a dense infiltrate of neutrophils without leukocytoclasia
Rheumatoid neutrophilic dermatosis
Produces urticarial lesions in association with SLE, RA, and secondary Sjogren syndrome, which lesions regress within 24 hours
Unlike urticaria, they are typically nonpruritic
Histopathologically, lesions show interstitial and perivascular neutrophlic infiltrate with leukocytoclasia without vasculitis, vacuolar alteration at the dermo-epidermal junction
Autoimmune neutrophilic dermatoses syndrome
Patients treated with _____ may develop an eruption that is clinically and histologically indistinguishable from psoriasis. This can occur in those receiving these agents for any condition, but those with RA appear to be at greatest risk
TNFalpha inhibitors
Most often affects men and smokers with longstanding disease, who are seropositive to rheumatoid factor and to cittrulinated peptides
Rheumatoid vasculitis
Remains the most consistently demonstrated environmental risk factor for rheumatoid vasculitis, particularly in male seropositive patients
Smoking
In rheumatoid vasculitis patients, cutaneous vasculitis was the most common presentation, followed by
Vasculitic neuropathy
Although complement levels are normal or elevated in RA, hypocomplementemia is often seen in patients with
Rheumatoid vasculitis
Rheumatoid vasculitis primarily affects small- to medium-sized vessels systemically and shares many features with _____, albeit without the development of microaneurysms
Polyarteritis nodosa
Minute digital ulcerations or petechiae and digital pulp papules
Manifestation of mild vasculitis and typically occur without systemic signs of vasculitis
Bywaters lesions
Should be suspected if deep liquefying ulcers with a characteristic purple, undermined border occur in patients with RA
Occurs more frequently and more severely in females
Pyoderma gangrenosum
Leg ulcers may also appear in patients with _____, a combination of chronic RA, hypersplenisms, and leukopenia
Felty syndrome
Synovial inflammation in RA usually results in warmth, but not _____ of the affected areas
Erythema
Characteristic involvement of the proximal interphalangeal and metacarpophalangeal joints with sparing of the distal interphalangeal joints
Hand and foot involvement is predominant
Symmetric and diffuse pattern
Rheumatoid arthritis
Characteristic deformities of RA include (ulnar/radial) deviation of the hand with (ulnar/radial) deviation of the digits
Radial
Ulnar
Hyperextension of the proximal interphalangeal joint and compensatory flexion of the distal interphalangeal joint
“Swan neck” deformity
Flexion contracture of the proximal interphalangeal joint and extension of the distal interphalangeal joint
Boutonniere deformity
An important posttranslational modification of protein is the conversion of _____ to its polar analog _____. This greatly enhances immune recognition of joint-associated proteins, which are selectively targetted by autoreactive T and B cells in patients with RA
Arginine
Citrulline
Antibodies that are highly specific for RA and can be found is approximately 50% of early RA patients
Predicts disease severity and radiologic damage
Anticitrullinated protein antibodies (ACPAs)
Process where the amino acid lysine is changed to become homocitrulline
Enhanced by smoking
Carbamylation
More than 100 genetic loci are associated with RA, the most important being within the HLA class II region, encoding the
HLA-DRB1 molecule
Autoantibody that reacts with the Fc portion of immunoglobulin G
Found in sera of 85% of patients with RA
Rheumatoid factor
More specific marker than rheumatoid factor, particularly in early disease
ACPAs
New recommendation for RA means that therapy with _____ should be started as soon as the diagnosis is made, with the aim of sustained remission or low disease activity
Disease-modifying antirheumatic drugs
Should be part of the first treatment strategy in RA, unless contraindicated
Methotrexate
Suggested as a first treatment strategy in RA when methotrexate is contraindicated
Leflunomide
Sulfasalazine
Should be considered when initiating or changing conventional DMARDs
Short-term glucocorticoids
Group of conditions encompassing all forms of arthritis of unknown etiology lasting for at least 6 weeks and with an onset before 16 years of age
Juvenile idiopathic arthirtis
Juvenile idiopathic arthiritis encompasses 7 entities
Systemic onset arthritis Oligoarthritis (persistent or extended) Rheumatoid factor-negative polyarthritis Rheumatoid factor-positive polyarthritis Psoriatic arthritis Enthesitis-related arthritis Undifferentiated
Of the types of JIA, only the _____ forms have skin findings
Systemic-onset JIA
Psoriatic arthiritis
There is increasing evidence that juvenile psoriatic arthritis is not a homogeneous disease entity, but includes at least 2 distinct subgroups
Same characteristics as early-onset antinuclear antibody-positive JIA
Spectrum of spondyloarthropathies
Systemic-onset JIA accounts for _____% of children with JIA
5% to 15%
The International League of Associations for Rheumatology criteria for sJIA require the presence of
Arthritis accompanied or preceded by a documented quotidian fever of at least 2 weeks duration
The fever of sJIA has a typical _____ pattern, with 1 or 2 daily spikes, up to 39C or higher, followed by rapid return to baseline
Intermittent
The erythematous, salmon pink, evanescent macular rash usually appears
With the fever
Arthritis of sJIA is often (symmetrical/asymmetrical) and (mono-/oligo-/polyarticular)
Symmetrical
Polyarticular
The eruption of sJIA is identical to that often seen in
Adult-onset Still disease
Usually affects boys older than age 6 years and presents with lower-limb asymmetrical arthritis associated with enthesitis
Later, these children can develop inflammatory lumbosacral pain and are at risk of developing acute anterior uveitis
Enthesitis-related arthritis
Secondary or acquired form of hemophagocytic lymphohistiocytosis (HLH)
Potentially life-threatening complication of rheumatic disorders, most commonly with sJIA and adult-onset Still disease
Macrophage activation syndrome
Often the heralding manifestation of macrophage activation syndrome
Change in the fever pattern from the intermittent spikes of sJIA to a continuous high level
Most widely used conventional DMARD in JIA
Methotrexate
Characterize a syndrome of seronegative polyarthritis, salmon-colored mostly macular and evanescent eruption, fever, and raised erythrocyte sedimentation rate, which along with neutrophilic leukocytosis, mirrors the presentation of sJIA
Adult-onset Still disease
Two serious complications associated with AOSD
Reactive hemophagocytic syndrome
Thrombotic thrombocytopenic purpura
An important newly recognized complication of AOSD is its association with
Malignancy
The malignancies associated with AOSD were 50% _____, 50% _____
Hematopoietic (mostly lymphomas) Solid tumors (breast, lung, esophagus, and liver angiosarcoma)
Rare but potentially life-threatening complication of AOSD that responds positively to corticosteroids and other immunomodulatory drugs
Myocarditis
Standard criteria set for AOSD
Yamaguchi criteria
A very elevated serum ferritin with a lowered concentration of glycosylated ferritin, is strongly suggestive of, but not specific for this diagnosis
AOSD
More specific for the diagnosis of AOSD
Fraction of glycosylated ferritin
In healthy individuals, 50% to 80% of serum ferritin is glycosylated, but this drops to _____% in patients with inflammatory diseases
20 to 50
Acute rheumatic fever is an inflammatory response to group A streptococcal infection, which typically occurs _____ after a throat infection
2 to 3 weeks
Most cases of ARF occur in
Children ages 5 to 15 years
Most probably involves cross-reactivity of streptococcal antibodies against myocardium, synovial tissue, and, in chorea, the basal ganglea`
RF
Diagnosis of initial acute rheumatic fever
2 major criteria or
1 major plus 2 minor criteria
Diagnosis of recurrent acute rheumativ fever
2 major criteria or
1 major plus 2 minor or
3 minor criteria
ARF major criteria
Carditis Chorea Erythema marginatum Subcutaneous nodules Arthritis
Rapid improvement with salicylates or NSAIDs is characterisitic
RF
Generally, the arthritis in ARF runs a self-limited course, even without therapy, lasting approximately
4 weeks
Y/N: Both erythema marginatum and subcutaneous nodules are rare in ARF
Yes - each occurring in less than 5% of cases
Much like the eruption in sJIA and Still disease, is evanescent, but differs by its tendency to develop annular or serpiginous erythema
Typically occurs on the torso, upper arms, and legs, and spares the face
Erythema marginatum
Typically less than 2 cm in diameter, firm, painless, and mobile nodules
Usually appear during the first weeks of the inflammatory phase and tend to localize over extensor surfaces
Subcutaneous nodules
Subcutaneous nodules often occur in association with
Carditis
Typically occurs after a longer latent period (up to 6 months) after a sterptococcal infection, by which time the other inflammatory features of rheumatic fever have resolved
Chorea
Treatment is first directed at eradication of group A beta-hemolytic streptococci from the oropharynx using
Phenoxymethylpenicillin (penicillin VK) 250 mg twice daily in children; 500mg twice daily in adolescents or
Single dose of IM benzathine penicillin followed by institution of long-term prophylaxis
Recommended alternative in instances of penicillin allergy
Erythromycin
