Rheumatology

Question 1

Inflammatory pain is stiffness that improves with activity; morning stiffness __1 hour. Mechanical pain is stiffness that worsens with activity; morning stiffness ___45 mins.

Answer 1

Inflammatory pain is stiffness that improves with activity; morning stiffness >1 hour. Mechanical pain is stiffness that worsens with activity; morning stiffness <45 mins.

Question 2

Juvenile Idiopathic Arthritis (JIA) (formerly known as juvenile rheumatoid arthritis) - SEE CHART

• Defined as follows:
  
  • Occurring before 16 years old
  • Persistent synovitis in >=1 joints
  • Synovitis for >=6 weeks
• Labs: Elevated ESR
  
  • Synovial fluid WBC counts, compromised mostly of lymphocytes, are usually between 2,000-30,000 cells/mL but can be as high as 100,000 cells/mL
• Clues for diagnosis of JIA:
  
  • Morning stiffness (min 15 mins) that improves with movement later throughout the day or after activity
  • Voluntary guarding of an inflamed joint.

Management

• Several categories of JIA may be associated with _____. Bc ocular inflammation in JIA is commonly asymptomatic, the AAP guidelines recommend that children with JIA undergo regular screening for uveitis with frequent ____ ophthalmologic evaluations.
• Although ____ testing is not useful for the diagnosis of JIA (40-50% can be ANA-negative), it is an important factor in the risk stratification of uveitis.
  
  • Band keratopathy is associated with Juvenile RA

Treatment

• ____ (naproxen, indomethacin, ibuprofen) are often used initially, typically with ____ (Disease-modifying antirheumatic drugs)
  
  • DMARD most commonly used is ___.
• Intraarticular injection of ___ (an injectable steroid) is an excellent local way of treating JIA, esp if only a “few” joints are affected.
• Biologic therapies
  
  • Test for latent TB infection, hepatitis B virus (HBV), and hepatitis C virus prior to initiating biologic therapy.
  • Once a pt is on biology therapy, avoid live attenuated vaccines.
  • TNF inhibitors (tumor necrosis factor inhibitors, TNFI)
    
    • Etanercept, adalimumab, infliximab
  • T-cell modulators (Abatacept)
  • IL-6 receptor blockers (tocilizumab)
  • IL-1 blockers (eg anakinra, canakinumab, rilonacept)
• Generally, do not use corticosteroids except for very severe disease, flares of disease, or systemic manifestations.
  
  • The use of systemic steroids is typically restricted to the management of the extra-articular manifestations of systemic JIA or as a bridge while awaiting the full effect of methotrexate.

Answer 2

Juvenile Idiopathic Arthritis (JIA) (formerly known as juvenile rheumatoid arthritis) - SEE CHART

• Defined as follows:
  
  • Occurring before 16 years old
  • Persistent synovitis in >=1 joints
  • Synovitis for >=6 weeks
• Labs: Elevated ESR
  
  • Synovial fluid WBC counts, compromised mostly of lymphocytes, are usually between 2,000-30,000 cells/mL but can be as high as 100,000 cells/mL
• Clues for diagnosis of JIA:
  
  • Morning stiffness (min 15 mins) that improves with movement later throughout the day or after activity
  • Voluntary guarding of an inflamed joint.

Management

• Several categories of JIA may be associated with uveitis. Bc ocular inflammation in JIA is commonly asymptomatic, the AAP guidelines recommend that children with JIA undergo regular screening for uveitis with frequent slit-lamp ophthalmologic evaluations.
• Although ANA testing is not useful for the diagnosis of JIA (40-50% can be ANA-negative), it is an important factor in the risk stratification of uveitis.
  
  • Band keratopathy is associated with Juvenile RA

Treatment

• NSAIDs (naproxen, indomethacin, ibuprofen) are often used initially, typically with DMARDs (Disease-modifying antirheumatic drugs)
  
  • DMARD most commonly used is methotrexate.
• Intraarticular injection of triamcinolone (an injectable steroid) is an excellent local way of treating JIA, esp if only a “few” joints are affected.
• Biologic therapies
  
  • Test for latent TB infection, hepatitis B virus (HBV), and hepatitis C virus prior to initiating biologic therapy.
  • Once a pt is on biology therapy, avoid live attenuated vaccines.
  • TNF inhibitors (tumor necrosis factor inhibitors, TNFI)
    
    • Etanercept, adalimumab, infliximab
  • T-cell modulators (Abatacept)
  • IL-6 receptor blockers (tocilizumab)
  • IL-1 blockers (eg anakinra, canakinumab, rilonacept)
• Generally, do not use corticosteroids except for very severe disease, flares of disease, or systemic manifestations.
  
  • The use of systemic steroids is typically restricted to the management of the extra-articular manifestations of systemic JIA or as a bridge while awaiting the full effect of methotrexate.

Question 3

JIA

• 7 subtypes
  
  • 1) Systemic: (sJIA)
    
    • ___ + daily ____ + _____ finding (rash, lymphadenopathy, hepatosplenomegaly, serositis, myocarditis)
    • Occurrence of daily fever, arthritis, and other systemic findings
      
      • The key is finding 1 or 2 fever spikes on a daily basis, which returns to normal without any antipyretics (Quotidian fever).
      • Rash is migratory with macular, pink-salmon coloring
        
        • Mild irritation, such as rubbing or scratching (Koebner phenomenon), may cause the rash to appear
      • ______ is the most common cardiac complication in pts with JIA.
    • Lab findings can be very abnormal
      
      • Occasional leukemoid reaction (>40,000 WBC/uL), thrombocytosis (occasionally >1 million cells/uL) and high CRP and ESR.
      • _____ levels that are very elevated (eg >5000-100,000 ng/mL or higher) raise suspicion of ____
  • 2 and 3) Polyarthritis: Rheumatoid Factor Positive or Rheumatoid Factor Negative (poJIA RF- and RF+)
    
    • Involves >=___ joints during the first 6 months and is found in 30-40% of those diagnosed with JIA.
    • RF-negative poJIA
      
      • 50-80% of children with RF-negative poJIA have a +ANA
        
        • Uveitis is typically asymptomatic; younger children <7 yo with a +ANA and poJIA, have intermediate risk of uveitis and should be monitored more closely.
        • Uveitis is less common with polyarticular compared to oligoarticular onset, affecting only 10-15% with +ANA.
    • RF-positive poJIA
      
      • RF+ is a poor prognostic finding and mandate aggressive management of the pt.
      • Anti-_____ antibodies, often seen in adult RA, are also detectable in a significant proportion of RF+ JIA pts.
      • RF+ and CCP+ antibodies indicate a worse prognosis
  • 4) Oligoarthritis: (oJIA)
    
    • Arthritis in less than ___ (<=4) joints during the first 6 mo of disease.
    • 2 subtypes of oJIA are defined by the course of the arthritis after 6 months of disease
      
      • Persistent oligoarthritis: When the child has only <4 joints involved throughout the course of disease.
      • Extended oligoarthritis (a worse prognosis): When the child develops disease in >5 joints after the first 6 months
    • Pt:
      
      • Asymptomatic _____ involvement is typical in pts with oJIA and is best diagnosed by MRI.
      • Remember: Pts with oligoarticular joint disease can have leg length discrepancies if the knees are involved (affected leg is longer initially, particularly in younger patients).
      • Asymptomatic anterior uveitis can occur in about 30% of pts with oJIA
        
        • ANA positivity predicts higher risk of developing uveitis.
    • Labs are nonspecific in oJIA
      
      • About 70% of children with oJIA have a +ANA in low titer (<1:320).
        
        • It is very important to know that a +ANA is not a diagnostic tool for JIA. It is used as a prognostic indicator for risk of uveitis in children with JIA.
    • Ophthalmologic screening with slit-lamp exam.
  • 5) Enthesitis-related arthritis (ERAs) (aka Spondyloarthritides)
    
    • The following are ERAs: Juvenile spondyloarthropathy; SEA syndrome (syndrome of seronegativity, enthesopathy, and arthropathy); HLA-B27-associated arthropathy and enthesopathy syndrome; oligoarticular-onset JIA “Type II”; juvenile ankylosing spondylitis
    • Definition:
      
      • Enthesitis and arthritis, or
      • Either enthesitis or arthritis with >2 of the following:
        
        • 1) History or presence of sacroiliac joint tenderness and/or inflammatory lumbosacral pain
        • 2) Presence of HLA-B27 antigen
        • 3) Onset of arthritis in a male >6 yo
        • 4) Acute symptomatic uveitis
        • 5) A 1st degree relative with ankylosing spondylitis, ERA, sacroiliitis with inflammatory bowel disease, or reactive arthritis.
    • Different characteristics compared to other childhood inflammatory arthritides:
      
      • Older children are affected more often
      • Males are more commonly affected
      • It is familial 10-20% of the time
      • Arthritis is typically peripheral with lower limb involvement in an asymmetric manner
      • Enthesitis is a common finding
    • Pt:
      
      • Children (usually boys) present with morning pain and stiffness that is relieved by playing or other activity.
        
        • Pain is predominantly in the joints or the LEs and is frequently in the lower back/buttocks and at the entheses of the heels, feet, and knees.
    • Labs: ESR is normal in 50% if pts and HLA-B27 is positive in 50-90%.
  • 6) Juvenile Psoriatic arthritis: (psJIA)
    
    • Defined by:
      
      • Arthritis and psoriasis, or
      • Arthritis and at least 2 of the following:
        
        • ___
        • ____
        • Family hx of ___
    • Pt:
      
      • Arthritis can precede the psoriasis by many years.
        
        • Arthritis develops in about 7% of pts with cutaneous psoriasis, but it is much more likely to develop (>30%) in those with psoriatic nail involvement.
        • ____ also typical, and this makes psoriatic arthritis unique compared to the other JIA subtypes.
      • Acute or chronic anterior uveitis is common, as is ANA+ (30-50% of pts).
    • Tx: Management is based on the severity of disease and the pt’s response to tx.
      
      • Pts with mild arthritis can be tx with a NSAID.
      • Pts who are not responsive to NSAIDs, or who have moderate-severe arthritis, should be started on a DMARD. The most commonly used DMARD for psoriatic arthritis is methotrexate.
  • 7) Undifferentiated (uJIA)

Answer 3

JIA

• 7 subtypes
  
  • 1) Systemic: (sJIA)
    
    • Arthritis in >1 joints + daily fever + systemic finding (rash, lymphadenopathy, hepatosplenomegaly, serositis, myocarditis)
    • Occurrence of daily fever, arthritis, and other systemic findings
      
      • The key is finding 1 or 2 fever spikes on a daily basis, which returns to normal without any antipyretics (Quotidian fever).
      • Rash is migratory with macular, pink-salmon coloring
        
        • Mild irritation, such as rubbing or scratching (Koebner phenomenon), may cause the rash to appear
      • Pericarditis is the most common cardiac complication in pts with JIA.
    • Lab findings can be very abnormal
      
      • Occasional leukemoid reaction (>40,000 WBC/uL), thrombocytosis (occasionally >1 million cells/uL) and high CRP and ESR.
      • Ferritin levels that are very elevated (eg >5000-100,000 ng/mL or higher) raise suspicion of MAS
  • 2 and 3) Polyarthritis: Rheumatoid Factor Positive or Rheumatoid Factor Negative (poJIA RF- and RF+)
    
    • Involves >=5 joints during the first 6 months and is found in 30-40% of those diagnosed with JIA.
    • RF-negative poJIA
      
      • 50-80% of children with RF-negative poJIA have a +ANA
        
        • Uveitis is typically asymptomatic; younger children <7 yo with a +ANA and poJIA, have intermediate risk of uveitis and should be monitored more closely.
        • Uveitis is less common with polyarticular compared to oligoarticular onset, affecting only 10-15% with +ANA.
    • RF-positive poJIA
      
      • RF+ is a poor prognostic finding and mandate aggressive management of the pt.
      • Anti-CCP (anticyclic citrullinated peptide) antibodies, often seen in adult RA, are also detectable in a significant proportion of RF+ JIA pts.
      • RF+ and CCP+ antibodies indicate a worse prognosis
  • 4) Oligoarthritis: (oJIA)
    
    • Arthritis in <5 (<=4) joints during the first 6 mo of disease.
    • 2 subtypes of oJIA are defined by the course of the arthritis after 6 months of disease
      
      • Persistent oligoarthritis: When the child has only <4 joints involved throughout the course of disease.
      • Extended oligoarthritis (a worse prognosis): When the child develops disease in >5 joints after the first 6 months
    • Pt:
      
      • Asymptomatic temporomandibular joint (TMJ) involvement is typical in pts with oJIA and is best diagnosed by MRI.
      • Remember: Pts with oligoarticular joint disease can have leg length discrepancies if the knees are involved (affected leg is longer initially, particularly in younger patients).
      • Asymptomatic anterior uveitis can occur in about 30% of pts with oJIA
        
        • ANA positivity predicts higher risk of developing uveitis.
    • Labs are nonspecific in oJIA
      
      • About 70% of children with oJIA have a +ANA in low titer (<1:320).
        
        • It is very important to know that a +ANA is not a diagnostic tool for JIA. It is used as a prognostic indicator for risk of uveitis in children with JIA.
    • Ophthalmologic screening with slit-lamp exam.
  • 5) Enthesitis-related arthritis (ERAs) (aka Spondyloarthritides)
    
    • The following are ERAs: Juvenile spondyloarthropathy; SEA syndrome (syndrome of seronegativity, enthesopathy, and arthropathy); HLA-B27-associated arthropathy and enthesopathy syndrome; oligoarticular-onset JIA “Type II”; juvenile ankylosing spondylitis
    • Definition:
      
      • Enthesitis and arthritis, or
      • Either enthesitis or arthritis with >2 of the following:
        
        • 1) History or presence of sacroiliac joint tenderness and/or inflammatory lumbosacral pain
        • 2) Presence of HLA-B27 antigen
        • 3) Onset of arthritis in a male >6 yo
        • 4) Acute symptomatic uveitis
        • 5) A 1st degree relative with ankylosing spondylitis, ERA, sacroiliitis with inflammatory bowel disease, or reactive arthritis.
    • Different characteristics compared to other childhood inflammatory arthritides:
      
      • Older children are affected more often
      • Males are more commonly affected
      • It is familial 10-20% of the time
      • Arthritis is typically peripheral with lower limb involvement in an asymmetric manner
      • Enthesitis is a common finding
    • Pt:
      
      • Children (usually boys) present with morning pain and stiffness that is relieved by playing or other activity.
        
        • Pain is predominantly in the joints or the LEs and is frequently in the lower back/buttocks and at the entheses of the heels, feet, and knees.
    • Labs: ESR is normal in 50% if pts and HLA-B27 is positive in 50-90%.
  • 6) Juvenile Psoriatic arthritis: (psJIA)
    
    • Defined by:
      
      • Arthritis and psoriasis, or
      • Arthritis and at least 2 of the following:
        
        • Dactylitis
        • Nail findings (pitting, oil spots, or onycholysis)
        • Family hx of psoriasis in at least one 1st degree relative.
    • Pt:
      
      • Arthritis can precede the psoriasis by many years.
        
        • Arthritis develops in about 7% of pts with cutaneous psoriasis, but it is much more likely to develop (>30%) in those with psoriatic nail involvement.
        • Distal interphalangeal (DIP) joint arthritis is also typical, and this makes psoriatic arthritis unique compared to the other JIA subtypes.
      • Acute or chronic anterior uveitis is common, as is ANA+ (30-50% of pts).
    • Tx: Management is based on the severity of disease and the pt’s response to tx.
      
      • Pts with mild arthritis can be tx with a NSAID.
      • Pts who are not responsive to NSAIDs, or who have moderate-severe arthritis, should be started on a DMARD. The most commonly used DMARD for psoriatic arthritis is methotrexate.
  • 7) Undifferentiated (uJIA)

Question 4

Macrophage Activation Syndrome (MAS)
- Children severely affected by sJIA can develop a life-threatening condition called macrophage activation syndrome, also known as acquired hemophagocytic syndrome.

• Causes:
  
  • Usual cause is uncontrolled _____
  • Can be caused by infections (EBV, parvovirus B19, and varicella) and drugs (sulfa drugs, NSAIDs)
• Path: Macrophages phagocytosis / eating bone marrow. Overactivation of T cells and macrophages.
• Pt:
  
  • Persistent fever
  • Hepatosplenomegaly
  • ______ (affecting at least 2 of the 3 cell lines)
  • Markedly high ferritin
  • Liver dysfunction marked by elevated LFTs, coagulopathy, low fibrinogen, and/or elevated triglycerides
  • Neurologic symptoms.
• HIGH ____, high CRP. Low ____, low fibrinogen
• Dx:
  
  • Hemophagocytosis by macrophages/histiocytes is evident on bone marrow biopsy, although not always present
• Tx: High-dose _____, IL-1 or IL-6 inhibitors, and/or cyclosporine can prevent life-threatening complications in MAS.

Answer 4

Macrophage Activation Syndrome (MAS)
- Children severely affected by sJIA can develop a life-threatening condition called macrophage activation syndrome, also known as acquired hemophagocytic syndrome.

• Causes:
  
  • Usual cause is uncontrolled sJIA
  • Can be caused by infections (EBV, parvovirus B19, and varicella) and drugs (sulfa drugs, NSAIDs)
• Path: Macrophages phagocytosis / eating bone marrow. Overactivation of T cells and macrophages.
• Pt:
  
  • Persistent fever
  • Hepatosplenomegaly
  • Cytopenias (affecting at least 2 of the 3 cell lines)
  • Markedly high ferritin
  • Liver dysfunction marked by elevated LFTs, coagulopathy, low fibrinogen, and/or elevated triglycerides
  • Neurologic symptoms.
• HIGH ferritin, high CRP. Low ESR, low fibrinogen
• Dx:
  
  • Hemophagocytosis by macrophages/histiocytes is evident on bone marrow biopsy, although not always present
• Tx: High-dose corticosteroids IV solumedrol, IL-1 or IL-6 inhibitors, and/or cyclosporine can prevent life-threatening complications in MAS.

Question 5

Henoch-Schonlein Purpura

• Path: ___-mediated leukocytoclastic vasculitis with neutrophil infiltration and deposits of immunoglobulins IgA and complement C3 in the small blood vessels.
  
  • Specific cause of unknown, but in 50% of cases, a URI precedes the disease
• Pt: Triad of ___, ___, ____
  
  • Skin lesions are present in all HSP patients (100%), and it is the presenting finding in about 50%: Palpable purpura (Nonblanching, nonpururitic) on dependent areas, such as legs and buttocks.
    
    • Angioedema sometimes precedes the rash.
  • 2nd most common: Joint involvement, occurring in 50-80%.
    
    • Periarthritis, with edema around the joints and inflammation involving the tendon sheaths, is the most common musculoskeletal manifestation.
  • Next most prevalent: GI manifestations
    
    • Abdominal pain that is colicky and sometimes involves vomiting as well.
    • Occult bleeding is common in those with abdominal pain, and melena can occur.
    • If abdominal pain is severe or persistent, perform US to evaluate for intussusception, which can occur in 2-14% of pts.
  • Renal disease similar to IgA nephropathy
    
    • Look for isolated microscopic hematuria or for hematuria and proteinuria.
  • Other manifestations: Orchitis and pulmonary hemorrhage.
• Lab to support but are nonspecific findings: Normal platelet count
• Dx: Clinical without confirmatory lab tests
• Tx: _______
  
  • Supportive (hydration and pain management (NSAIDs to help joint pain (but use w caution in pts with renal insufficiency and GI disease)) for most pts since usually resolves spontaneously.
  • All children should be followed with UA and BP every 1-2 weeks for the first 1-2mo after presentation
    
    • Order serial urinalysis for at least 3-6 months after diagnosis to monitor for renal involvement.
• Prognosis: ______. The disease tends to be self-limited and lasts 4 weeks in about 65% of children.
  
  • HSP recurs in up to 40% of pts from 6 weeks to 2 year after initial presentation.

Answer 5

Henoch-Schonlein Purpura

• Path: IgA-mediated leukocytoclastic vasculitis with neutrophil infiltration and deposits of immunoglobulins IgA and complement C3 in the small blood vessels.
  
  • Specific cause of unknown, but in 50% of cases, a URI precedes the disease
• Pt: Triad of purpura, arthritis, abdominal pain
  
  • Skin lesions are present in all HSP patients (100%), and it is the presenting finding in about 50%: Palpable purpura (Nonblanching, nonpururitic) on dependent areas, such as legs and buttocks.
    
    • Angioedema sometimes precedes the rash.
  • 2nd most common: Joint involvement, occurring in 50-80%.
    
    • Periarthritis, with edema around the joints and inflammation involving the tendon sheaths, is the most common musculoskeletal manifestation.
  • Next most prevalent: GI manifestations
    
    • Abdominal pain that is colicky and sometimes involves vomiting as well.
    • Occult bleeding is common in those with abdominal pain, and melena can occur.
    • If abdominal pain is severe or persistent, perform US to evaluate for intussusception, which can occur in 2-14% of pts.
  • Renal disease similar to IgA nephropathy
    
    • Look for isolated microscopic hematuria or for hematuria and proteinuria.
  • Other manifestations: Orchitis and pulmonary hemorrhage.
• Lab to support but are nonspecific findings: Normal platelet count
• Dx: Clinical without confirmatory lab tests
• Tx: No specific therapy
  
  • Supportive (hydration and pain management (NSAIDs to help joint pain (but use w caution in pts with renal insufficiency and GI disease)) for most pts since usually resolves spontaneously.
  • All children should be followed with UA and BP every 1-2 weeks for the first 1-2mo after presentation
    
    • Order serial urinalysis for at least 3-6 months after diagnosis to monitor for renal involvement.
• Prognosis: Excellent. The disease tends to be self-limited and lasts 4 weeks in about 65% of children.
  
  • HSP recurs in up to 40% of pts from 6 weeks to 2 year after initial presentation.

Question 6

Granulomatosis with Polyangiitis (Wegener’s)

• Very rare in children.
• Systemic vasculitis with necrotizing granuloma of small-sized vessels involving the upper and lower respiratory tracts and the kidney - pulmonary-renal syndrome.
• Pt: ___, ___, ___
  
  • Nasal deformity (saddle nose) and subglottic stenosis can also occur in children with GPA and, less commonly, in relapsing polychondritis.
  • Lung findings (nodules, infiltrates, hemoptysis, or pleuritis) or reported in 70% of children with GPA.
  • Ocular findings (conjunctivitis, dacryocystitis, scleritis, and proptosis) occur in 15-20% of these children.
  • Renal involvement is uncommon in these children at presentation but eventually occurs in 60-70%.
• _____ positive is found in >90% of pts with diffuse disease and only ~50% of those with limited (ie no renal involvement) disease.
  
  • When positive in a patient with GPA, the offending antibody is always c-ANCA (96%), whereas polyarteritis is usually p-ANCA.
• Dx: Confirm from either ____ of nasal membrane or an open lung biopsy
• Tx: _____ with or without corticosteroids.
  
  • Consider using steroids, methotrexate (especially for limited disease), rituximab, and cyclophosphamide.
  • Chronic therapy with TMP/SMX prevents relapses and decreases the risk for Pneumocystis jiroveci pneumonia (PCP).

Answer 6

Granulomatosis with Polyangiitis (Wegener’s)

• Very rare in children.
• Systemic vasculitis with necrotizing granuloma of small-sized vessels involving the upper and lower respiratory tracts and the kidney - pulmonary-renal syndrome.
• Pt: Sinus, lungs, kidneys
  
  • Nasal deformity (saddle nose) and subglottic stenosis can also occur in children with GPA and, less commonly, in relapsing polychondritis.
  • Lung findings (nodules, infiltrates, hemoptysis, or pleuritis) or reported in 70% of children with GPA.
  • Ocular findings (conjunctivitis, dacryocystitis, scleritis, and proptosis) occur in 15-20% of these children.
  • Renal involvement is uncommon in these children at presentation but eventually occurs in 60-70%.
• c-ANCA positive is found in >90% of pts with diffuse disease and only ~50% of those with limited (ie no renal involvement) disease.
  
  • When positive in a patient with GPA, the offending antibody is always c-ANCA (96%), whereas polyarteritis is usually p-ANCA.
• Dx: Confirm from either biopsy of nasal membrane or an open lung biopsy
• Tx: Cyclophosphamide with or without corticosteroids.
  
  • Consider using steroids, methotrexate (especially for limited disease), rituximab, and cyclophosphamide.
  • Chronic therapy with TMP/SMX prevents relapses and decreases the risk for Pneumocystis jiroveci pneumonia (PCP).

Question 7

Kawasaki Disease (Mucocutaneous lymph node syndrome)

• 2nd most common vasculitis in childhood.
• It is the leading cause of acquired heart disease in children in the US.
• Path: Unknown.
• Pt:
  
  • Pathognomonic cardiac manifestation (and the one of most concern) is _______ that develop in 20-25% of inadequate treated cases.
  • ______ is the main cause of death and most commonly occurs during the 1st year from the onset of illness.
  • Look for other findings, including aseptic meningitis, acute uveitis, diarrhea, and mild obstructive jaundice with elevated transaminases, hydrops of the gallbladder, polyarthritis/polyarthralgia, and sterile pyuria.
• Labs:
  
  • Elevation of the ____ can help differentiate Kawasaki disease from other fever and rash syndromes that do not have gallbladder involvement.

Answer 7

Kawasaki Disease (Mucocutaneous lymph node syndrome)

• 2nd most common vasculitis in childhood.
• It is the leading cause of acquired heart disease in children in the US.
• Path: Unknown.
• Pt:
  
  • Pathognomonic cardiac manifestation (and the one of most concern) is coronary artery aneurysms that develop in 20-25% of inadequate treated cases.
  • Myocardial infarction is the main cause of death and most commonly occurs during the 1st year from the onset of illness.
  • Look for other findings, including aseptic meningitis, acute uveitis, diarrhea, and mild obstructive jaundice with elevated transaminases, hydrops of the gallbladder, polyarthritis/polyarthralgia, and sterile pyuria.
• Labs:
  
  • Elevation of the gamma-glutamyl transferase (GGT) can help differentiate Kawasaki disease from other fever and rash syndromes that do not have gallbladder involvement.

Question 8

Kawasaki

• Dx: Diagnosis of exclusion; based on clinical and lab criteria
  
  • Presence of fever >5 days (in 100%) with at least __ of the 5 criteria:
    
    • ____
    • ____
    • ____
    • ____
    • ____
• Diagnosis with <4 of the 5 criteria is possible if coronary aneurysm is demonstrated on echo or angiography. Fever is an absolute requirement.
• Dx: “Incomplete Kawasaki’s” is 5 days of fever w <4 signs
  
  • Patients who have been febrile for >=5 days but who fill <=3 diagnostic criteria should have supporting laboratory studies (___ or ___) ordered and should be reexamined the following day.
• Work-up: CBC with diff, CMP, CRP, ESR, and urinalysis

Answer 8

Kawasaki

• Dx: Diagnosis of exclusion; based on clinical and lab criteria
  
  • Presence of fever >5 days (in 100%) with at least 4 of the 5 criteria:
    
    • Polymorphous rash usually macular or maculopapular erythematous, but any rash except vesicles, bullae, scaling, crusting (in >90%)
    • Conjunctival injection without drainage (in 80-90%)
    • Mucous membrane changes: Erythema, cracked, and peeling lips. Strawberry tongue. Injected pharynx (in 80-90%)
    • Peripheral extremity changes with erythema and edema of the hands and feet and later desquamation (in approx 80%)
    • Cervical lymphadenopathy (at least 1 node >1.5cm) (in approx 50%)
• Diagnosis with <4 of the 5 criteria is possible if coronary aneurysm is demonstrated on echo or angiography. Fever is an absolute requirement.
• Dx: “Incomplete Kawasaki’s” is 5 days of fever w <4 signs
  
  • Patients who have been febrile for >=5 days but who fill <=3 diagnostic criteria should have supporting laboratory studies (C REACTIVE PROTEIN or ESR) ordered and should be reexamined the following day.
• Work-up: CBC with diff, CMP, CRP, ESR, and urinalysis

Question 9

Kawasaki

• Tx:
  
  • Initially _____ 2g/kg as single dose over 8-12 hours administered within first ____ days of fever onset reduces risk of CAAs from 25-2%
  • _____ (reduces systemic inflammation) initially at antiinflammatory high dose 30-50mg/kg divided q6hrs (or 80-100mg/kg/day PO in 4 divided doses). Best if tx given within first _____ days of illness. Measure child’s temperature q6hr until 48 hours after last fever. Once fever has abated for ____ hours, aspirin dose decreases to antiplatelet/antithrombotic dose ___mg/kg daily for at least ___ weeks or longer if CAA persists on 6 week echocardiogram until assured there is no cardiac involvement.
• NO live virus vaccines for ____ mo after given IVIG
• ___ VACCINE (administered IM) must be given to patients with Kawsaki disease if they are placed on long-term aspirin therapy. This is done to prevent the complications of _____ syndrome in the setting of aspirin therapy.
• The risk of recurrent Kawasaki disease occurring weeks to months later is approximately 2%.
• Complications: Coronary artery aneurysm (CAA) most commonly occurs ____ weeks after onset of fever
  
  • Perform baseline echo on admission, repeat at ___ weeks and at ___ weeks
  • Myocardial infarction, if it occurs, usually does so during the 1st year after the onset of illness.

Answer 9

Kawasaki

• Tx:
  
  • Initially IVIG 2g/kg as single dose over 8-12 hours administered within first 7-10 days of fever onset reduces risk of CAAs from 25-2%
  • Aspirin (reduces systemic inflammation) initially at antiinflammatory high dose 30-50mg/kg divided q6hrs (or 80-100mg/kg/day PO in 4 divided doses). Best if tx given within first 7-10 days of illness. Measure child’s temperature q6hr until 48 hours after last fever. Once fever has abated for 48 hours, aspirin dose decreases to antiplatelet/antithrombotic dose 3-5mg/kg daily for at least 6 weeks or longer if CAA persists on 6 week echocardiogram until assured there is no cardiac involvement.
• NO live virus vaccines for 11 mo after given IVIG
• Inactivated INFLUENZA VACCINE (administered IM) must be given to patients with Kawsaki disease if they are placed on long-term aspirin therapy. This is done to prevent the complications of Reye syndrome in the setting of aspirin therapy.
• The risk of recurrent Kawasaki disease occurring weeks to months later is approximately 2%.
• Complications: Coronary artery aneurysm (CAA) most commonly occurs 1-4 weeks after onset of fever
  
  • Perform baseline echo on admission, repeat at 2 weeks and at 6 weeks
  • Myocardial infarction, if it occurs, usually does so during the 1st year after the onset of illness.

Question 10

Polyarteritis Nodosa
- Inflammation of medium-sized arteries and results in a focal segmental necrotizing vasculitis. Leads to classic “_____” of vessel pattern.

• Path: Exact etiology is unknown, although documented cases have occurred after hepatitis B or strep infection
  
  • One thing to look for - ____! Occurs most commonly in those with concomitant _____ infection.
  • There is an absence of _____ involvement.
• Dx:
  
  • Usually based on criteria:
    
    • Skin lesions (eg purpura, livedo)
    • Testicular pain/orchitis
    • Mononeuritis multiplex (presenting as a foot drop)
    • Renal involvement
    • Hypertension
    • Evidence of hepatitis B
    • Weight loss
    • Biopsy or angiographic findings.
  • Confirm with biopsy of affected tissue (eg skin, kidney, muscle, sural nerve) or angiograph showing stenosis and aneurysm formation.
• Tx: ____ and immunosuppressive agents
• Prognosis is poor without aggressive treatment.
  
  • Causes aneurysm and stenosis, resulting in hematuria and renovascular hypertension. Does NOT cause _____, unlike MPA.

Answer 10

Polyarteritis Nodosa
- Inflammation of medium-sized arteries and results in a focal segmental necrotizing vasculitis. Leads to classic “beading” of vessel pattern.

• Path: Exact etiology is unknown, although documented cases have occurred after hepatitis B or strep infection
  
  • One thing to look for - Orchitis! Occurs most commonly in those with concomitant hepatitis B infection.
  • There is an absence of lung involvement.
• Dx:
  
  • Usually based on criteria:
    
    • Skin lesions (eg purpura, livedo)
    • Testicular pain/orchitis
    • Mononeuritis multiplex (presenting as a foot drop)
    • Renal involvement
    • Hypertension
    • Evidence of hepatitis B
    • Weight loss
    • Biopsy or angiographic findings.
  • Confirm with biopsy of affected tissue (eg skin, kidney, muscle, sural nerve) or angiograph showing stenosis and aneurysm formation.
• Tx: Steroids and immunosuppressive agents
• Prognosis is poor without aggressive treatment.
  
  • Causes aneurysm and stenosis, resulting in hematuria and renovascular hypertension. Does NOT cause glomerulonephritis, unlike MPA.

Question 11

Microscopic Polyangiitis (MPA)

• ______ associated (perinuclear antibodies to MPO [myeloperoxidase]) small-vessel vasculitis without granuloma formation.
• Causes ______.
• Glomerular involvement is extensive, causing rapidly progressive glomerulonephritis and a _____ syndrome (resulting in pulmonary hemorrhage) similar to GPA.

Answer 11

Microscopic Polyangiitis (MPA)

• P-ANCA associated (perinuclear antibodies to MPO [myeloperoxidase]) small-vessel vasculitis without granuloma formation.
• Causes glomerulonephritis.
• Glomerular involvement is extensive, causing rapidly progressive glomerulonephritis and a pulmonary-renal syndrome (resulting in pulmonary hemorrhage) similar to GPA.

Question 12

Takayasu Arteritis (Pulseless Disease)
- It leads to arteritis of the aorta and its major branches, resulting in weak or absent pulses in the UEs. 

• Pt:
  
  • A simple, yet very useful test to help identify this as a possible diagnosis is to perform 4-extremity BPs.
  • Inflammatory prepulseless stage
  • Noninflammatory occlusive stage
• Dx: Proposed criteria
  
  • Angiographic abnormalities (as demonstrated by CR or MRA) of the aorta or main branches, plus at least 1 of the following:
    
    • 1) Decreased peripheral pulses and/or claudication of the extremities
    • 2) Blood pressure difference of >___ mmHg between arms
    • 3) Audible bruits over aorta and/or major branches
    • 4) Hypertension
• Tx: ____ and ____ are the mainstays of therapy.

Answer 12

Takayasu Arteritis (Pulseless Disease)
- It leads to arteritis of the aorta and its major branches, resulting in weak or absent pulses in the UEs. 

• Pt:
  
  • A simple, yet very useful test to help identify this as a possible diagnosis is to perform 4-extremity BPs.
  • Inflammatory prepulseless stage
  • Noninflammatory occlusive stage
• Dx: Proposed criteria
  
  • Angiographic abnormalities (as demonstrated by CR or MRA) of the aorta or main branches, plus at least 1 of the following:
    
    • 1) Decreased peripheral pulses and/or claudication of the extremities
    • 2) Blood pressure difference of >10 mmHg between arms
    • 3) Audible bruits over aorta and/or major branches
    • 4) Hypertension
• Tx: Glucocorticoids and cyclophosphamide are the mainstays of therapy.

Question 13

Behcet Disease
- Unlike any other vasculitis in that it can involve blood vessels of any size and type

• Pt:
  
  • Look for the classic triad of:
    
    • 1) ____
      
      • Key finding is recurrent buccal aphthous ulcers, which are found in nearly 100% of patients.
    • 2) ___
    • 3) ___
  • Skin lesions (including erythema nodosum and necrotic folliculitis) are common.
  • You occasionally see a positive ____ test - prick the skin with a needle, and after 48 hours you see a pustule or papule surrounded by redness.
• Dx: _____. Requires observation of recurrent oral ulceration at least 3x over a 1-year period plus at least 2 of the following: Recurrent genital ulcerations, eye lesions, skin lesions, or positive pathergy test.
• Tx: _____

Answer 13

Behcet Disease
- Unlike any other vasculitis in that it can involve blood vessels of any size and type

• Pt:
  
  • Look for the classic triad of:
    
    • 1) Oral ulcers (painful, recurrent),
      
      • Key finding is recurrent buccal aphthous ulcers, which are found in nearly 100% of patients.
    • 2) Genital ulcers (painful, recurrent), and
    • 3) Inflammatory eye disease
  • Skin lesions (including erythema nodosum and necrotic folliculitis) are common.
  • You occasionally see a positive pathergy test - prick the skin with a needle, and after 48 hours you see a pustule or papule surrounded by redness.
• Dx: Clinical. Requires observation of recurrent oral ulceration at least 3x over a 1-year period plus at least 2 of the following: Recurrent genital ulcerations, eye lesions, skin lesions, or positive pathergy test.
• Tx: Corticosteroids (oral or topical)

Question 14

CNS vasculitis - Inflammatory disease affecting the blood vessels of the brain.

• Childhood primary angiitis of the CNS (cPACNS) is the primary form of this vasculitis.
• Pt: Arterial stroke in children.
• Dx: __ is considered the gold standard for diagnosis but is rather invasive.
• Tx: For small-vessel and medium-to-large vessel progressive cPACNS, typically high-dose ___ and cyclophosphamide.

Answer 14

CNS vasculitis - Inflammatory disease affecting the blood vessels of the brain.

• Childhood primary angiitis of the CNS (cPACNS) is the primary form of this vasculitis.
• Pt: Arterial stroke in children.
• Dx: Angiography is considered the gold standard for diagnosis but is rather invasive.
• Tx: For small-vessel and medium-to-large vessel progressive cPACNS, typically high-dose steroids and cyclophosphamide.

Question 15

Systemic Lupus Erythematosus (SLE)

• Pt:
  
  • Common manifestations are arthritis (80-90%), rash (70-80%), nephritis (50-60%).
    
    • Unlike JIA, in SLE the XRs are ___ and _____ even after years of arthritis. Over time, poJIA can show osteopenia and joint damage on XR.
    • Avascular necrosis (AVN) is fairly common
  • _____ rash, the hallmark of cutaneous SLE, is the most frequent skin manifestation of SLE. Also discoid rash and/or photosensitivity.
    
    • Alopecia is fairly common
    • Oral lesions/ulcerations are usually painless
  • Renal involvement (75% cases of pediatric SLE), usually develops within the 1st year of symptom onset.
    
    • Pt: May present with hypertension, hematuria and proteinuria, nephrotic syndrome, elevated creatinine or rapidly progressive glomerulonephritis.
  • May present with pericardial effusion (friction rub, positional chest pain)
  • SLE affects both __ AND ___ more frequently than any other collagen vascular disease (60%, while scleroderma affects lung alone more than any other collagen vascular disease (100%, but no pleural changes))
  • CNS manifestations:
    
    • Note: SLE is the most common cause of ___ in the US. Chorea in SLE is often associated with antiphospholipid antibodies.
    • Order serum antiribosomal P antibodies and antineuronal antibodies (from CSF) to help diagnose lupus psychosis or lupus cerebritis.
  • Cardiopulmonary:
    
    • Most common cardiac abnormality in children with SLE is pericarditis.
      
      • Libman-Sacks endocarditis (nonbacterial endocarditis with verrucous vegetations) is associated with SLE and antiphospholipid antibodies.
    • Pulmonary manifestations can vary from as severe as pulmonary hemorrhage or infection
      
      • Pleural disease is very common and can present as pleuritis or pleural effusion.
  • Hematologic manifestations: Cytopenias are common.
    
    • Up to 75% of pts are found to have 1 or more cytopenias
    • Lupus anticoagulant causes an in vitro prolongation of _____ but not prothrombin time (PT).

Answer 15

Systemic Lupus Erythematosus (SLE)

• Pt:
  
  • Common manifestations are arthritis (80-90%), rash (70-80%), nephritis (50-60%).
    
    • Unlike JIA, in SLE the XRs are nonerosive and nondeforming even after years of arthritis. Over time, poJIA can show osteopenia and joint damage on XR.
    • Avascular necrosis (AVN) is fairly common
  • Malar butterfly rash, the hallmark of cutaneous SLE, is the most frequent skin manifestation of SLE. Also discoid rash and/or photosensitivity.
    
    • Alopecia is fairly common
    • Oral lesions/ulcerations are usually painless
  • Renal involvement (75% cases of pediatric SLE), usually develops within the 1st year of symptom onset.
    
    • Pt: May present with hypertension, hematuria and proteinuria, nephrotic syndrome, elevated creatinine or rapidly progressive glomerulonephritis.
  • May present with pericardial effusion (friction rub, positional chest pain)
  • SLE affects both lung AND pleura more frequently than any other collagen vascular disease (60%, while scleroderma affects lung alone more than any other collagen vascular disease (100%, but no pleural changes))
  • CNS manifestations:
    
    • Note: SLE is the most common cause of chorea in the US. Chorea in SLE is often associated with antiphospholipid antibodies.
    • Order serum antiribosomal P antibodies and antineuronal antibodies (from CSF) to help diagnose lupus psychosis or lupus cerebritis.
  • Cardiopulmonary:
    
    • Most common cardiac abnormality in children with SLE is pericarditis.
      
      • Libman-Sacks endocarditis (nonbacterial endocarditis with verrucous vegetations) is associated with SLE and antiphospholipid antibodies.
    • Pulmonary manifestations can vary from as severe as pulmonary hemorrhage or infection
      
      • Pleural disease is very common and can present as pleuritis or pleural effusion.
  • Hematologic manifestations: Cytopenias are common.
    
    • Up to 75% of pts are found to have 1 or more cytopenias
    • Lupus anticoagulant causes an in vitro prolongation of partial thromboplastin time (PTT) but not prothrombin time (PT).

Question 16

SLE

• Labs:
  
  • Positive ANA in almost all pediatric patients with SLE (98-99%).
  • Anti-dsDNA antibodies: 2nd most common (60-70%)
    
    • The presence of dsDNA AND anti-Smith antibodies correlates with ____ involvement in SLE.
  • Anti-Smith antibodies: Found in about 33% of SLE patients.
  • Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, and beta-2-glycoprotein-1 antibodies): Found in up to 50% of lupus patients.
    
    • These antibodies affect pathways of coagulation and increase the risk of miscarriages, thrombocytopenia, livedo reticularis, Libman-Sacks endocarditis, and blood clots in about 25% of pts.
  • Anti-U1 RNP antibodies: Least produced.
  • Hypocomplementemia:
    
    • C3 and C4 often decline with active disease
    • If you suspect lupus but ANA is negative but fulfill other aspects, get a CH50. If CH50 is low, can have a complement deficiency that mimics lupus.
• Dx based on SLICC criteria (2012)
  
  • Presence of >4 of the 17 criteria, with at least 1 clinical and 1 immunologic criteria, OR biopsy-proven lupus nephritis and ANA or dsDNA
  • Clinical criteria
    
    • 1. Acute cutaneous lupus
    • 2. Chronic cutaneous lupus
    • 3. Oral and nasal ulcers
    • 4. Serositis
    • 5. Joint disease
    • 6. Renal
    • 7. Hemolytic anemia
    • 8. Leukopenia or lymphopenia on 1 or more occasions (*in the absence of offending drugs and associated known metabolic derangements)
    • 9. Thrombocytopenia (*)
    • 10. Neurologic (*)
    • 11. Nonscarring alopecia
  • Immunologic criteria:
    
    • 12. ANA
    • 13. Anti-dsDNA
    • 14. Anti-Sm
    • 15. Antiphospholipid
    • 16. Direct Coombs test
    • 17. Low complement levels: C3, C4, or CH50
• Work-up
  
  • Renal biopsy (with histologic, immunofluorescent, and electron micrographic analyses) is required if lupus nephritis is suspected

Answer 16

SLE

• Labs:
  
  • Positive ANA in almost all pediatric patients with SLE (98-99%).
  • Anti-dsDNA antibodies: 2nd most common (60-70%)
    
    • The presence of dsDNA AND anti-Smith antibodies correlates with renal involvement in SLE.
  • Anti-Smith antibodies: Found in about 33% of SLE patients.
  • Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, and beta-2-glycoprotein-1 antibodies): Found in up to 50% of lupus patients.
    
    • These antibodies affect pathways of coagulation and increase the risk of miscarriages, thrombocytopenia, livedo reticularis, Libman-Sacks endocarditis, and blood clots in about 25% of pts.
  • Anti-U1 RNP antibodies: Least produced.
  • Hypocomplementemia:
    
    • C3 and C4 often decline with active disease
    • If you suspect lupus but ANA is negative but fulfill other aspects, get a CH50. If CH50 is low, can have a complement deficiency that mimics lupus.
• Dx based on SLICC criteria (2012)
  
  • Presence of >4 of the 17 criteria, with at least 1 clinical and 1 immunologic criteria, OR biopsy-proven lupus nephritis and ANA or dsDNA
  • Clinical criteria
    
    • 1. Acute cutaneous lupus
    • 2. Chronic cutaneous lupus
    • 3. Oral and nasal ulcers
    • 4. Serositis
    • 5. Joint disease
    • 6. Renal
    • 7. Hemolytic anemia
    • 8. Leukopenia or lymphopenia on 1 or more occasions (*in the absence of offending drugs and associated known metabolic derangements)
    • 9. Thrombocytopenia (*)
    • 10. Neurologic (*)
    • 11. Nonscarring alopecia
  • Immunologic criteria:
    
    • 12. ANA
    • 13. Anti-dsDNA
    • 14. Anti-Sm
    • 15. Antiphospholipid
    • 16. Direct Coombs test
    • 17. Low complement levels: C3, C4, or CH50
• Work-up
  
  • Renal biopsy (with histologic, immunofluorescent, and electron micrographic analyses) is required if lupus nephritis is suspected

Question 17

SLE

• Tx:
  
  • Low-dose aspirin
  • ________
    
    • Data shows that continued use of antimalarial therapy prevents disease flares (a 3x reduction in the rate of flares when compared to those who discontinued hydroxychloroquine), decreases mortality in adult SLE patients, lowers serum cholesterol levels, and decreases the risk for neonatal lupus in mothers who take the drug.
    • Screen for these rare complications 1-2x/year with eye examinations performed by an ophthalmologist.
  • Prednisone
    
    • Know common side effects from long-term use of steroids:
      
      • AVN
      • Osteoporosis with fracture or vertebral collapse
      • Growth failure
      • Glaucoma and cataracts
      • Diabetes mellitus
      • HTN
      • Accelerated atherosclerosis
      • Infection
  • Belimumab
  • Rheumatologists use multiple DMARDs and immunomodulators that are not FDA approved to manage their patients: Mycophenolate mofetil, methotrexate, azathioprine, cyclophosphamide, cyclosporine, leflunomide, rituximab.
    
    • Cyclophosphamide (CYP)
      
      • The risk of bladder carcinoma is directly related to the development of ____ that is a result of bladder wall toxicity from this agent.
        
        • To prevent cystitis, administer ___ with IV cyclophosphamide
• Prognosis
  
  • SLE is an independent RF for _____.
  • Late morbidity and early mortality are due to premature atherosclerotic disease >10-20 years after onset.
  • SLE is a significant RF for the development of premature coronary atherosclerosis and CAD.

Answer 17

SLE

• Tx:
  
  • Low-dose aspirin
  • Hydroxychloroquine
    
    • Data shows that continued use of antimalarial therapy prevents disease flares (a 3x reduction in the rate of flares when compared to those who discontinued hydroxychloroquine), decreases mortality in adult SLE patients, lowers serum cholesterol levels, and decreases the risk for neonatal lupus in mothers who take the drug.
    • Screen for these rare complications 1-2x/year with eye examinations performed by an ophthalmologist.
  • Prednisone
    
    • Know common side effects from long-term use of steroids:
      
      • AVN
      • Osteoporosis with fracture or vertebral collapse
      • Growth failure
      • Glaucoma and cataracts
      • Diabetes mellitus
      • HTN
      • Accelerated atherosclerosis
      • Infection
  • Belimumab
  • Rheumatologists use multiple DMARDs and immunomodulators that are not FDA approved to manage their patients: Mycophenolate mofetil, methotrexate, azathioprine, cyclophosphamide, cyclosporine, leflunomide, rituximab.
    
    • Cyclophosphamide (CYP)
      
      • The risk of bladder carcinoma is directly related to the development of hemorrhagic cystitis that is a result of bladder wall toxicity from this agent.
        
        • To prevent cystitis, administer mesna with IV cyclophosphamide
• Prognosis
  
  • SLE is an independent RF for coronary artery disease.
  • Late morbidity and early mortality are due to premature atherosclerotic disease >10-20 years after onset.
  • SLE is a significant RF for the development of premature coronary atherosclerosis and CAD.

Question 18

Neonatal Lupus Erythematosus

• Path: Develops as a result of transplacental passage of maternal autoantibodies.
  
  • 50% of these mothers do not know they have these autoantibodies, typically anti-___ (anti-Ro) and anti-___ (anti-La) antibodies.
• Pt: Rash, cytopenias, hepatitis, and, most importantly, bradycardia from ______
  
  • Cutaneous findings include periorbital erythema (often referred to as raccoon eyes) and round or annular, often atrophic, pink patches and plaques.
• Most noncardiac features resolve within 6 months as maternal antibodies disappear.
• _____ syndrome can develop in children up to 12 months of age; bc of this, an ECG should be repeated at least once by 12 months of age.
• Tx:
  
  • If there is evidence for cardiac conduction abnormalities, _____ is often given to decrease the risk for complete heart block and pacemaker dependency.
  • For cutaneous lesions, tx is conservative: Photoprotection, topical steroids, and emollients.
  • Although culprit maternal antibodies are cleared by around 6 months of age, the sequelae of neonatal lupus can be lifelong and severe.

Answer 18

Neonatal Lupus Erythematosus

• Path: Develops as a result of transplacental passage of maternal autoantibodies.
  
  • 50% of these mothers do not know they have these autoantibodies, typically anti-SSA (anti-Ro) and anti-SSB (anti-La) antibodies.
• Pt: Rash, cytopenias, hepatitis, and, most importantly, bradycardia from congenital complete heart block
  
  • Cutaneous findings include periorbital erythema (often referred to as raccoon eyes) and round or annular, often atrophic, pink patches and plaques.
• Most noncardiac features resolve within 6 months as maternal antibodies disappear.
• Prolonged QTc syndrome can develop in children up to 12 months of age; bc of this, an ECG should be repeated at least once by 12 months of age.
• Tx:
  
  • If there is evidence for cardiac conduction abnormalities, dexamethasone is often given to decrease the risk for complete heart block and pacemaker dependency.
  • For cutaneous lesions, tx is conservative: Photoprotection, topical steroids, and emollients.
  • Although culprit maternal antibodies are cleared by around 6 months of age, the sequelae of neonatal lupus can be lifelong and severe.

Question 19

Mixed Connective Tissue Disease

• Pt:
  
  • Raynaud phenomenon, fever, arthritis, dorsal hand edema, rash, and myositis.
  • Joint abnormalities are seen in 60-90% of children.
  • Over time, MCTD progresses like scleroderma, and many pts develop ______.
• Dx: High-titer antibodies against ______ (Distinctive autoantibody!)
• Tx: As in SLE, use ____.
• Mortality: Often occurs due to chronic interstitial lung disease or pulmonary HTN

Answer 19

Mixed Connective Tissue Disease

• Pt:
  
  • Raynaud phenomenon, fever, arthritis, dorsal hand edema, rash, and myositis.
  • Joint abnormalities are seen in 60-90% of children.
  • Over time, MCTD progresses like scleroderma, and many pts develop restrictive lung disease.
• Dx: High-titer antibodies against U1 RNP autoantigen (Distinctive autoantibody!)
• Tx: As in SLE, use antimalarials.
• Mortality: Often occurs due to chronic interstitial lung disease or pulmonary HTN

Question 20

Sjogren Syndrome
- Path: Autoimmune-mediated chronic inflammation of the lacrimal and salivary glands leads to the characteristic clinical features.

• Pt:
  
  • ___, ___, and an ____
  • Suspect in a child with recurrent parotitis in whom infection has been excluded
• Consider the following for diagnosis:
  
  • Inflamed and dry eyes (keratoconjunctivitis sicca)
  • Dryness of the mouth (xerostomia)
  • Lymphocytic infiltrate on minor salivary gland biopsy
  • Elevated titer of ___ (70%) and/or ___ (50%)
• ACR/EULAR 2016 Classification Criteria for primary Sjogren’s syndrome:
  
  • +SSA (Ro) (3 points)
  • Focal lymphocytic sialadenitis focus score >1 foci/4 mm2 (3 points)
  • Abnormal ocular staining score >5 (1 point)
  • Schirmer’s test <5 mm/5 min (1 point)
  • Unstim salivary flow <0.1 ml/min (1 point)
  • Signs/symptoms >4 meet criteria, sensitivity 96%, specificity 95%
• Tx:
  
  • Agents that increase moisture: artificial tears for the eyes, artificial saliva, and pilocarpine to stimulate exocrine secretions
  • Antimalarial agents can be used for skin rashes and joint symptoms
• Children generally do well, but pts with Sjogren’s are at increased risk for _______, esp mucosa-associated lymphoid tissue (MALT) lymphoma and non-Hodgkin B-cell lymphomas.
• Note: Children born to mothers with SS who have Ro (SSA) and/or La (SSB) antibodies are also at risk for developing neonatal lupus.

Answer 20

Sjogren Syndrome
- Path: Autoimmune-mediated chronic inflammation of the lacrimal and salivary glands leads to the characteristic clinical features.

• Pt:
  
  • Dryness of the mouth (xerostomia) and eyes (keratoconjunctivitis sicca), enlargement of the parotid glands, and an increase in dental caries
  • Suspect in a child with recurrent parotitis in whom infection has been excluded
• Consider the following for diagnosis:
  
  • Inflamed and dry eyes (keratoconjunctivitis sicca)
  • Dryness of the mouth (xerostomia)
  • Lymphocytic infiltrate on minor salivary gland biopsy
  • Elevated titer of anti-Ro/SSA (70%) and/or anti-La/SSB (50%)
• ACR/EULAR 2016 Classification Criteria for primary Sjogren’s syndrome:
  
  • +SSA (Ro) (3 points)
  • Focal lymphocytic sialadenitis focus score >1 foci/4 mm2 (3 points)
  • Abnormal ocular staining score >5 (1 point)
  • Schirmer’s test <5 mm/5 min (1 point)
  • Unstim salivary flow <0.1 ml/min (1 point)
  • Signs/symptoms >4 meet criteria, sensitivity 96%, specificity 95%
• Tx:
  
  • Agents that increase moisture: artificial tears for the eyes, artificial saliva, and pilocarpine to stimulate exocrine secretions
  • Antimalarial agents can be used for skin rashes and joint symptoms
• Children generally do well, but pts with Sjogren’s are at increased risk for lymphoma, esp mucosa-associated lymphoid tissue (MALT) lymphoma and non-Hodgkin B-cell lymphomas.
• Note: Children born to mothers with SS who have Ro (SSA) and/or La (SSB) antibodies are also at risk for developing neonatal lupus.

Question 21

Juvenile Dermatomyositis
- Systemic connective tissue disorder with chronic skeletal muscle and skin inflammation

• Pt: ___ and ____
  
  • Muscle weakness: Always proximal and symmetric
  • Rashes can very:
    
    • Characteristics rash: ___ rash (red-violet discoloration / scaly patches of the eyelids +/- edema) and/or ___ papules (papular red plaques over the dorsal surface of the finger joints) are found in most children
    • ___ sign (pink patches in a shawl- or cape-like distribution on the shoulders and back)
    • Calcinosis cutis and skin ulcerations can also occur and are bad prognostic signs.
  • Nearly 70% of pts have arthralgias.
    
    • When true arthritis occurs, oligoarthritis (affecting ~65%) is more common than polyarthritis (30-35%).
  • Ulcerative skin disease is a poor prognostic sign and can portend GI vasculitis - one of the most serious, life-threatening complications
  • Dystrophic calcification (calcinosis cutis) of the skin, subcutaneous tissue, and fascia occurs in 33% of affected pts.
  • Lipodystrophy
• Dx:
  
  • Presence of heliotrope rash or Gottron papules is required.
  • Definite dx = Plus at least 3 of the following 4 findings
  • Probably dx = Plus at least 2 of the following 4 findings
  • 1) _____
  • 2) Elevated____
  • 3) ____ abnormalities
    
    • a. Small amplitude, short duration, polyphasic motor-unit potentials
    • b. Fibrillations, positive sharp waves, increased insertional irritability
    • c. Spontaneous, bizarre, high-frequency discharges
  • 4) ____abnormalities of
    
    • a. Degeneration
    • b. Regeneration
    • c. Necrosis
    • d. Phagocytosis
    • e. Interstitial mononuclear cell infiltrate
• ______, demonstrating inflammation as symmetrical muscle edema, has become the preferred modality over EMG since EMG is invasive and uncomfortable.
• Tx:
  
  • Begin primary therapy with ____ 2-3 mg/kg/day.
  • 2nd line therapies and therapies for severe exacerbations
    
    • Includes IV methylprednisolone, IVIG, methotrexate, cyclosporine, and AZP.
  • If pts do not respond, try 3rd line therapy; combine 2nd line therapies plus:
    
    • Other immunomodulators (anti-TNFi and rituximab)
    • Or IV cyclophosphamide
• Childhood dermatomyositis rarely predisposes to malignancy unlike adult dermatomyositis.

Answer 21

Juvenile Dermatomyositis
- Systemic connective tissue disorder with chronic skeletal muscle and skin inflammation

• Pt: Rash and muscle weakness.
  
  • Muscle weakness: Always proximal and symmetric
  • Rashes can very:
    
    • Characteristics rash: Heliotrope rash (red-violet discoloration / scaly patches of the eyelids +/- edema) and/or Grotton papules (papular red plaques over the dorsal surface of the finger joints) are found in most children
    • Shawl sign (pink patches in a shawl- or cape-like distribution on the shoulders and back)
    • Calcinosis cutis and skin ulcerations can also occur and are bad prognostic signs.
  • Nearly 70% of pts have arthralgias.
    
    • When true arthritis occurs, oligoarthritis (affecting ~65%) is more common than polyarthritis (30-35%).
  • Ulcerative skin disease is a poor prognostic sign and can portend GI vasculitis - one of the most serious, life-threatening complications
  • Dystrophic calcification (calcinosis cutis) of the skin, subcutaneous tissue, and fascia occurs in 33% of affected pts.
  • Lipodystrophy
• Dx:
  
  • Presence of heliotrope rash or Gottron papules is required.
  • Definite dx = Plus at least 3 of the following 4 findings
  • Probably dx = Plus at least 2 of the following 4 findings
  • 1) Symmetric proximal muscle weakness
  • 2) Elevated CPK, aldolase, LDH (marker for muscle), or transaminases (marker for muscle)
  • 3) EMG abnormalities
    
    • a. Small amplitude, short duration, polyphasic motor-unit potentials
    • b. Fibrillations, positive sharp waves, increased insertional irritability
    • c. Spontaneous, bizarre, high-frequency discharges
  • 4) Muscle biopsy abnormalities of
    
    • a. Degeneration
    • b. Regeneration
    • c. Necrosis
    • d. Phagocytosis
    • e. Interstitial mononuclear cell infiltrate
• MRI of the thigh muscles, demonstrating inflammation as symmetrical muscle edema, has become the preferred modality over EMG since EMG is invasive and uncomfortable.
• Tx:
  
  • Begin primary therapy with prednisone 2-3 mg/kg/day.
  • 2nd line therapies and therapies for severe exacerbations
    
    • Includes IV methylprednisolone, IVIG, methotrexate, cyclosporine, and AZP.
  • If pts do not respond, try 3rd line therapy; combine 2nd line therapies plus:
    
    • Other immunomodulators (anti-TNFi and rituximab)
    • Or IV cyclophosphamide
• Childhood dermatomyositis rarely predisposes to malignancy unlike adult dermatomyositis.

Question 22

Systemic Scleroderma (Sclerosis)

• 2 separate subtypes
  
  • 1) Diffuse cutaneous scleroderma: Proximal and distal skin involvement with internal organ dysfunction of the GI tract, lung, heart, and kidney
    
    • Anti-_____ is seen more often
  • 2) Limited cutaneous scleroderma: Formerly known as CREST syndrome - c___, R___, e__, s__, and t___
    
    • _____ +
• Pt:
  
  • Raynaud phenomenon (spasm of the digital arteries with blanching and numbness or pain of the fingers, often precipitated by cold)
    
    • Classic Raynaud’s is triphasic; white, blue, and red on rewarming
  • GI tract is commonly affected, particularly the distal esophagus where systemic scleroderma affects distal smooth muscle
  • Lung involvement
    
    • __ occurs, which leads to R heart failure
    • Scleroderma affects ___ alone
      
      • 1) Interstitial fibrosis
      • 2) Intimal proliferation
        
        • Intimal proliferation in the pulmonary artery causes pulmonary HTN out of proportion to the pulmonary disease. Intimal proliferation - not the ILD - causes the real pulmonary problem
  • Renal crisis. Managing HTN with ACE inhibitors
• Dx: Dependent on findings of sclerodactyly (stiffness and tightness of the skin of the fingers), nail bed capillary findings showing periungual tortuous dilated loops (referred to as nailfold capillaroscopy), and internal organ involvement.
• Lab testing:
  
  • 80% of pts have a nucleolar or speckled ANA
  • 50% have antibodies to SCL-70 (topoisomerase 1)
  • Anticentromere antibodies, if they occur, are seen with limited cutaneous scleroderma and primary biliary cirrhosis.
• Esophageal manometry is the most sensitive test for esophageal abnormalities
• Tx: Supportive
  
  • Raynaud phenomenon responds to ___ (nifedipine) and____ (doxazosin).
  • ____ to prevent (and treat) renal crisis
  • Corticosteroids are relatively contraindicated due to the increased risk of renal crisis.

Answer 22

Systemic Scleroderma (Sclerosis)

• 2 separate subtypes
  
  • 1) Diffuse cutaneous scleroderma: Proximal and distal skin involvement with internal organ dysfunction of the GI tract, lung, heart, and kidney
    
    • Anti-SCL-70+ (topoisomerase I) is seen more often
  • 2) Limited cutaneous scleroderma: Formerly known as CREST syndrome - calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias
    
    • Anticentromere +
• Pt:
  
  • Raynaud phenomenon (spasm of the digital arteries with blanching and numbness or pain of the fingers, often precipitated by cold)
    
    • Classic Raynaud’s is triphasic; white, blue, and red on rewarming
  • GI tract is commonly affected, particularly the distal esophagus where systemic scleroderma affects distal smooth muscle
  • Lung involvement
    
    • Pulmonary HTN occurs, which leads to R heart failure
    • Scleroderma affects lung alone
      
      • 1) Interstitial fibrosis
      • 2) Intimal proliferation
        
        • Intimal proliferation in the pulmonary artery causes pulmonary HTN out of proportion to the pulmonary disease. Intimal proliferation - not the ILD - causes the real pulmonary problem
  • Renal crisis. Managing HTN with ACE inhibitors
• Dx: Dependent on findings of sclerodactyly (stiffness and tightness of the skin of the fingers), nail bed capillary findings showing periungual tortuous dilated loops (referred to as nailfold capillaroscopy), and internal organ involvement.
• Lab testing:
  
  • 80% of pts have a nucleolar or speckled ANA
  • 50% have antibodies to SCL-70 (topoisomerase 1)
  • Anticentromere antibodies, if they occur, are seen with limited cutaneous scleroderma and primary biliary cirrhosis.
• Esophageal manometry is the most sensitive test for esophageal abnormalities
• Tx: Supportive
  
  • Raynaud phenomenon responds to calcium channel blockers (nifedipine) and alpha-blockers (doxazosin).
  • ACE inhibitors to prevent (and treat) renal crisis
  • Corticosteroids are relatively contraindicated due to the increased risk of renal crisis.

Question 23

Localized Scleroderma (Morphea, plaque morphea, linear scleroderma, deep morphea)

• Pt: During the active phase, lesions have a red border and a white “waxy” center. As the lesions become inactive, they can be either hyper- or hypopigmented.
  
  • Linear scleroderma - most common localized scleroderma seen in children
    
    • Streaks involving the face or scalp are known as en coupe de sabre, like a depression due to a dueling stroke from a sword.
• Tx:
  
  • Benign condition that resolves in 3-5 years, self-limited; however can lead to significant limb growth abnormalities when there is extensive subdermal involvement; this sometimes requires systemic therapy including steroids and/or methotrexate.

Answer 23

Localized Scleroderma (Morphea, plaque morphea, linear scleroderma, deep morphea)

• Pt: During the active phase, lesions have a red border and a white “waxy” center. As the lesions become inactive, they can be either hyper- or hypopigmented.
  
  • Linear scleroderma - most common localized scleroderma seen in children
    
    • Streaks involving the face or scalp are known as en coupe de sabre, like a depression due to a dueling stroke from a sword.
• Tx:
  
  • Benign condition that resolves in 3-5 years, self-limited; however can lead to significant limb growth abnormalities when there is extensive subdermal involvement; this sometimes requires systemic therapy including steroids and/or methotrexate.

Question 24

AMYLOIDOSIS
- Amyloid accumulation occurs with many diseases including infectious diseases (tuberculosis, leprosy, and chronic osteomyelitis), familial Mediterranean fever, IBD, Behcet disease, and SLE.

• Pt:
  
  • ____ disease is the most prevalent and serious manifestation of amyloid deposition. Pts present with proteinuria, with rapid progression to nephrotic-range proteinuria, and then eventually renal failure.
• Look for markedly increased ESR, CRP, and serum amyloid A levels
• The key is to find amyloid deposition in tissue.
  
  • Can see amyloid by staining with ___ under polarized light and then looking for ______ birefringence.
• Prevention is more effective than treatment

Answer 24

AMYLOIDOSIS
- Amyloid accumulation occurs with many diseases including infectious diseases (tuberculosis, leprosy, and chronic osteomyelitis), familial Mediterranean fever, IBD, Behcet disease, and SLE.

• Pt:
  
  • Renal disease is the most prevalent and serious manifestation of amyloid deposition. Pts present with proteinuria, with rapid progression to nephrotic-range proteinuria, and then eventually renal failure.
• Look for markedly increased ESR, CRP, and serum amyloid A levels
• The key is to find amyloid deposition in tissue.
  
  • Can see amyloid by staining with Congo red under polarized light and then looking for green-yellow birefringence.
• Prevention is more effective than treatment

Question 25

RECURRENT FEVERS

- Recurrent fever syndromes: >__ episodes of unexplained fever in a __-month period

Answer 25

RECURRENT FEVERS

- Recurrent fever syndromes: >3 episodes of unexplained fever in a 6-month period

Question 26

Fever of unknown origin
- Fever of unknown origin (documented fever for >___ weeks with no etiology identified on routine evaluation) or fever >38.3 daily for at least 8 days

Answer 26

Fever of unknown origin
- Fever of unknown origin (documented fever for >2 weeks with no etiology identified on routine evaluation) or fever >38.3 daily for at least 8 days

Question 27

PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis)

• Relatively common disorder with no known genetic cause. No recognizable inheritance pattern. Not prominent in any ethnic group is not associated with amyloid deposition.
• Benign syndrome that occurs in children between the ages of 6mo and 7 years (mean age ~3 years).
• Pt:
  
  • In contrast to FMF, the fever lasts longer in PFAPA - from _____ days.
  • The periodicity is usually ~4 weeks and is unaccompanied by any sign of infection.
• No lab tests to diagnose.
• Dx: Based on fever pattern and physical exam
• Tx:
  
  • Flares respond quickly to ____ (1mg/kg/dose x 3 doses given 12 hours apart), which also helps to point to PFAPA as the disease.

Answer 27

PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis)

• Relatively common disorder with no known genetic cause. No recognizable inheritance pattern. Not prominent in any ethnic group is not associated with amyloid deposition.
• Benign syndrome that occurs in children between the ages of 6mo and 7 years (mean age ~3 years).
• Pt:
  
  • In contrast to FMF, the fever lasts longer in PFAPA - from 5-7 days.
  • The periodicity is usually ~4 weeks and is unaccompanied by any sign of infection.
• No lab tests to diagnose.
• Dx: Based on fever pattern and physical exam
• Tx:
  
  • Flares respond quickly to prednisone (1mg/kg/dose x 3 doses given 12 hours apart), which also helps to point to PFAPA as the disease.

Question 28

Familial Mediterranean Fever
- _____inheritance? disorder mainly seen in Armenians, Turks, Levantine Arabs, and Sephardic Jews.

• Path: Responsible gene (MEFV) is localized in chromosome ____. The product of this gene is an amino-acid protein called pyrine (aka marenostrin)
• Pt:
  
  • Most children have attacks of fever that can last from several hours to ___ days.
  • Fever typically recurs in predictable cycles; for 3-5 days every month for 1 patient, or several times a year for another pt.
  • Severe _____ occurs with the fever.
• Dx: Clinical pattern, family hx, and response to colchicine.
• Tx:
  
  • Daily _____, which treats acute attacks, prevents future attacks, and prevents development of amyloidosis.
    
    • Most common side effects are ___ and ____ (particularly if renal disease is present)
  • _____ is a high concern for those not treated.

Answer 28

Familial Mediterranean Fever
- Autosomal recessive disorder mainly seen in Armenians, Turks, Levantine Arabs, and Sephardic Jews.

• Path: Responsible gene (MEFV) is localized in chromosome 16. The product of this gene is an amino-acid protein called pyrine (aka marenostrin)
• Pt:
  
  • Most children have attacks of fever that can last from several hours to 5 days.
  • Fever typically recurs in predictable cycles; for 3-5 days every month for 1 patient, or several times a year for another pt.
  • Severe abdominal pain occurs with the fever.
• Dx: Clinical pattern, family hx, and response to colchicine.
• Tx:
  
  • Daily colchicine, which treats acute attacks, prevents future attacks, and prevents development of amyloidosis.
    
    • Most common side effects are diarrhea and bone marrow suppression (particularly if renal disease is present)
  • Amyloidosis is a high concern for those not treated.

Question 29

TRAPS (TNF receptor-1 associated periodic syndrome, formerly known as familial Hiberanian fever of familial periodic fever)
- ____inheritance? disorder with incomplete penetrance.

• Path: Due to genetic defect in the gene that encodes the 55-kDa receptor for TNF
• Pt:
  
  • Episodes last longer than those of PFAPA - a min of 5 days and commonly longer than ___ weeks
  • Conjunctivitis and periorbital edema are common
  • ____ can occur and can be confused with FMF, but the fever episodes are much more prolonged in TRAPS.
• Tx:
  
  • ___, ____, etanercept, anakinra. Does not respond to colchicine.
  • _____ is a potential consequence so it is importance to diagnose and treat appropriately.

Answer 29

TRAPS (TNF receptor-1 associated periodic syndrome, formerly known as familial Hiberanian fever of familial periodic fever)
- Autosomal dominant disorder with incomplete penetrance.

• Path: Due to genetic defect in the gene that encodes the 55-kDa receptor for TNF
• Pt:
  
  • Episodes last longer than those of PFAPA - a min of 5 days and commonly longer than 2 weeks
  • Conjunctivitis and periorbital edema are common
  • Abdominal pain can occur and can be confused with FMF, but the fever episodes are much more prolonged in TRAPS.
• Tx:
  
  • NSAIDs, prednisone, etanercept, anakinra. Does not respond to colchicine.
  • Amyloidosis is a potential consequence so it is importance to diagnose and treat appropriately.

Question 30

Hyper-IgD Syndrome
- ____inheritance? disorder

• Path: Due to a mutation in the MVK gene that encodes mevalonate kinase, which likely results in excess production of IL-1
• Pt:
  
  • ____ episodes usually occur every 1-2 months.
  • Abdominal pain, nausea/vomiting, and nondestructive large-joint arthritis.
  • Can have a diffuse nonmigratory erythematous macular rash.
  • Lymphadenopathy, headaches, oral/vaginal ulcers, and splenomegaly also can occur during febrile episodes.
• Characteristically, IgD is often elevated (>100 IU/mL) but not always, and IgA is also elevated in most cases.
  
  • This helps differentiate this disease from other periodic fever syndromes.
• Tx: Colchicine, prednisone, IVIG, NSAIDs, etanercept, and anakinra.
  
  • Amyloidosis is rare in this disorder

Answer 30

Hyper-IgD Syndrome
- Autosomal recessive disorder

• Path: Due to a mutation in the MVK gene that encodes mevalonate kinase, which likely results in excess production of IL-1
• Pt:
  
  • Fever episodes usually occur every 1-2 months.
  • Abdominal pain, nausea/vomiting, and nondestructive large-joint arthritis.
  • Can have a diffuse nonmigratory erythematous macular rash.
  • Lymphadenopathy, headaches, oral/vaginal ulcers, and splenomegaly also can occur during febrile episodes.
• Characteristically, IgD is often elevated (>100 IU/mL) but not always, and IgA is also elevated in most cases.
  
  • This helps differentiate this disease from other periodic fever syndromes.
• Tx: Colchicine, prednisone, IVIG, NSAIDs, etanercept, and anakinra.
  
  • Amyloidosis is rare in this disorder

Question 31

Cryopyrin-Associated Periodic Fever Syndromes (CAPS)

• Group of autoinflammatory diseases with an autosomal dominant inheritance with variable expression
• 3 periodic fever syndromes resulting from inheritable abnormalities in cryopyrin (CIAS1 gene).
  
  • FCAS: Familial cold autoinflammatory syndrome
  • Muckle-Wells syndrome
  • NOMID: Neonatal-onset multisystem inflammatory disease
• Pt:
  
  • These disorders have overlapping clinical presentations, including fever, acute-phase inflammation, a neutrophilic urticarial skin rash, and joint involvement.
• Dx: Genetic testing.
• Tx:
  
  • Targeted inhibition of the IL-1 pathway has resulted in new treatments for these diseases
    
    • Cryopyrin is involved with the activation of IL-1beta.
  • Approved drugs include rilonacept, anakinra, and canakinumab.

Answer 31

Cryopyrin-Associated Periodic Fever Syndromes (CAPS)

• Group of autoinflammatory diseases with an autosomal dominant inheritance with variable expression
• 3 periodic fever syndromes resulting from inheritable abnormalities in cryopyrin (CIAS1 gene).
  
  • FCAS: Familial cold autoinflammatory syndrome
  • Muckle-Wells syndrome
  • NOMID: Neonatal-onset multisystem inflammatory disease
• Pt:
  
  • These disorders have overlapping clinical presentations, including fever, acute-phase inflammation, a neutrophilic urticarial skin rash, and joint involvement.
• Dx: Genetic testing.
• Tx:
  
  • Targeted inhibition of the IL-1 pathway has resulted in new treatments for these diseases
    
    • Cryopyrin is involved with the activation of IL-1beta.
  • Approved drugs include rilonacept, anakinra, and canakinumab.

Question 32

Cyclic neutropenia

• Consider cyclic neutropenia (immunodeficiency syndrome) in evaluation of recurrent fevers
• ____inheritance? or sporadic in inheritance
• Pt: Fever, malaise, lymphadenopathy, and mouth sores.
• Absolute neutrophil counts of less than ___ cells/uL occur every ___ days (range 14-36 days) like clockwork, with each episode lasting ___ days.
• Dx: Blood counts 3x/week every 6-8 weeks is sometimes necessary to make the diagnosis.

Answer 32

Cyclic neutropenia

• Consider cyclic neutropenia (immunodeficiency syndrome) in evaluation of recurrent fevers
• Autosomal dominant or sporadic in inheritance
• Pt: Fever, malaise, lymphadenopathy, and mouth sores.
• Absolute neutrophil counts of <500 cells/uL occur every 21 days (range 14-36 days) like clockwork, with each episode lasting 3-10 days.
• Dx: Blood counts 3x/week every 6-8 weeks is sometimes necessary to make the diagnosis.