Pediatric Lupus

Irit Tirosh 2016

1-מקרה

, כ"בריאה בד, שנים 17י בת .א•

כתפיים, ברכיים, שורשי כפות ידיים, אצבעות ידיים -שבועות כאבים במפרקים 3•

38מאתמול חום •

פ הלחיים וגשר האף"ע אריתמטוטיתמהבוקר פריחה •

100% סטורציה, 104/63ד "ל, 112דופק , 37.1חום : סימנים חיוניים•

.של שורשי כפות ידיים וברכיים ארתריטיס. ללא פריחה אחרת Malar rash -בבדיקתה•

יתר הבדיקה תקינה

-בדיקות מעבדה

200kטסיות תקינות , 10אנמיה , 600 לימפופניה, 3000 לויקופניה: ספירה•

תקינות טרנסאמינזות, תפקודי כליה ואלקטרוליטים תקינים: כימיה•

CRP 10, 70 -שקיעה•

תקין -שתן•

• ANA- 1:320

C3 80, C4 6 -משלים נמוך•

חיובי ANAו לימפופניה/לויקופניה, פריחת פרפר, ארתריטיס -על בסיס לופוסאבחנה של •

2-מקרה

, כ"בריא בד, שנים 12בן •

מזה חודשיים צווארית לימפאדנופתיה•

חום מזה כחודש•

ג בחודשיים האחרונים"ק 10ירידה במשקל כ •

טסיות תקינות , נורמו-נורמו 11המוגלובין , 590 לימפופניה ,3000 לויקפניה: ספירה•

שתן תקין , 80שקיעה , CRP 30, כימיה תקינה•

צילום חזה תקין•

במראה תקין, הגדלת בלוטות בצוואר ובבטן -USב •

קליטה בקשריות לימפה מעל ומתחת לסרעפת PET-CTב •

.וברטונלה ברוצלה, ,EBV, CMV, HIV, בירור זיהומי שלילי כולל שחפת•

.ראקטיביתבלוטה -ביופסיה מבלוטה•

ומשלים ANAנשלח •

המשך -2מקרה

פרכוסים וירידה במצב ההכרה•

C3 40, C4 4משלים נמוך •

•ANA 1:160חיובי

•Anti-dsDNA חיובי

חיובי anti-dsDNA, חיובי ANA, פרכוסים, לימפופניהעל בסיס לופוסאבחנה של •

3-מקרה

ברקע קומה נמוכה, שנים 13ס בן .י•

חודש וחצי כאבי בטן•

מבוקר קבלתו בצקת סביב העיניים•

תקינה סטורציה, 80דופק , 120/70לחץ דם , 37חום -סימנים חיוניים•

בדיקה גופנית תקינה למעט בצקת סביב העיניים•

. 120שקיעה , תקין CRP, 2.4כימיה תקינה למעט אלבומין , ספירת דם תקינה•

283טריגליצרידים , 357כולסטרול •

שתן מיקרוסקופ , 8 קראטינין/יחס חלבון, 4+חלבון -שתן -בבדיקת השתן במעבדה•קאסטיםללא 20HPFאריתרוציטים

C3 88, C4 6משלים נמוך •

המשך -3מקרה

•ANA 1:160

•Anti-dsDNAחיובי

4קלאס נפריטיס לופוסאבחנה של -ביופסיית כליה•

anti-dsDNAו ANA, כליה ביופסיתעל בסיס לופוסאבחנה של •

הפרצופים 1000המחלה בעלת -לופוס

pSLEpSLEpSLEpSLE ----EpidemiologyEpidemiologyEpidemiologyEpidemiology

• 20% of SLE cases are diagnosed during the first 2 decades of life

• Pediatric SLE average age of onset 12 years.

• 60% of pSLE after age 10 years, 35% between 5- 10 years, and 5% before age 5

• Before puberty M:F ratio is 1:3, after puberty 1:9

• pSLE incidence 6.0- 18.9 :100,000 in white girls; 20-30 in African American.

• High incidence in Hispanic, Native American, Pacific Islander, Asian.

• Classification criteria- same as adults

• pSLE- more abrupt in onset, with higher rates of organ involvement, more aggressive clinical course

• 5-year survival rate for pSLE approaches 100% ;10-year survival rate is 86%.

PathophysiologyPathophysiologyPathophysiologyPathophysiology

• Combination of hormonal and environmental factors in a genetically predisposed individual.

PathophysiologyPathophysiologyPathophysiologyPathophysiology

• Genetic factors:• 10% of patients with SLE have a first-degree relative who has SLE.

• HLA class II alleles DR2 and DR3 contribute to disease susceptibility in some patients

• pSLE risk alleles- P-selectin gene, il-1 receptor-associated kinase 1 gene, TNFRSF6 and interferon regulatory factor 5 gene.

• Congenital complement deficiencies account for about 1% pSLE.

• In C1q deficiency there is 90% chance of having a lupus-like illness early in life.

• C2, C4 and C1s or C1r deficiency, are also associated with early onset SLE

• Environmental factors:• Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased

incidence of SLE

• Hormonal factors:• oestrogen administration (17-β-estradiol) in a lupus prone mice model showed disease

progression

PathogenesisPathogenesisPathogenesisPathogenesis

• Defects in apoptosis

• Impaired clearance of the apoptotic material by the innate immune system

• B-cell hyperactivity and loss of tolerance

PathogenesisPathogenesisPathogenesisPathogenesis

• Abnormal apoptosis �

• Apoptotic material includes intracellular antigens which are exposed to the immune system �

• Activation of innate immune cells and autoreactive B cells �

• B-cell activation and expression of B-cell survival molecule receptor BAFF and APRIL

• Polyclonal B-cell activation �

• Production of autoantibodies directed against nuclear, cytoplasmic and plasma membrane antigens.

• Antinuclear antibodies bind to the nuclear material and result in immune complex deposition in tissues� multi-organ damage.

• B cells also present autoantigens to T cells and producing pro-inflammatory cytokines.

PathogenesisPathogenesisPathogenesisPathogenesis----2222

• Abnormal apoptosis�

• Activation of the plasmocytoid dendritic cells�

• Production of large amounts of type I interferon (IFN).

• IFN has multiple immunological functions, including promotion and differentiation of B cells, immunoglobulin switch, production of autoantibodies and an increased survival of activated B and T lymphocytes.

• IFN type I trigger the externalization of floating nets of chromatin fibres by neutrophils- neutrophil extracellular traps (NETs), a process known as NETosis. This results in a self-perpetuating cycle of pro-inflammatory debris leading to more pro inflammatory debris

• IFN levels are high in sera of patients with SLE with a good correlation between serum IFN titers and disease activity

Clinical presentationClinical presentationClinical presentationClinical presentation

• Variable

• Common signs and symptoms at disease onset- fatigue, fever, weight loss, lymphadenopathy, hepatosplenomegaly

• Delay in diagnosis 1m-3.3 y, median 4 months

MucocutaneousMucocutaneousMucocutaneousMucocutaneous involvementinvolvementinvolvementinvolvement

• In up to 90% of patients with pSLE.

• Three rashes described in the SLE classification criteria:

1. The malar/“butterfly” rash -the most common, sparing the nasolabial folds.

2. Discoid lupus- erythematous rash, primarily face, ears, and scalp. Fewer than 5% of patients who have isolated discoid SLE will progress to SLE.

3. Photosensitivity

MucocutaneousMucocutaneousMucocutaneousMucocutaneous involvementinvolvementinvolvementinvolvement

• Vasculitic rashes- palmar erythema, tender skin nodules, purpura, ulcerations.

• Palatal ulceration -usually painless.

• Raynaud phenomenon- triphasic color change (white,blue, red). Triggers- exposure to cold, cigarettes, caffeine, extreme emotion.

• Livedo reticularis occurs in <10% of patients with pSLE. Often is associated with antiphospholipid antibodies.

• Alopecia- may be one of the presenting manifestations, classically in the frontal area

Musculoskeletal involvementMusculoskeletal involvementMusculoskeletal involvementMusculoskeletal involvement

• Common- Arthralgia and arthritis. are very common in pSLE. Nonerosive. Usually symmetric large and small joints, the knees, wrists, ankles, and fingers.

• Jacoud arthropathy - ulnar deviation of the second to fifth fingers and subluxation of the metacarpophalangeal Joints

• Myalgia and myositis.

Renal involvementRenal involvementRenal involvementRenal involvement

• Greatest contributor to morbidity and mortality in the pSLE.

• Up to 65% of patients with pSLE are affected, usually within the first year of diagnosis.

• Renal disease may manifest as proteinuria, microscopic hematuria, hypertension, elevated BUN/Cr.

• Immune complexes deposit in the mesangium and subendothelial space�activation of complement and an influx of inflammatory cells.

• Active urine sediment- red blood cells, white blood cells, and cellular and granular casts

• Low complement levels (C3, C4), elevated anti-dsDNA levels, and proteinuria.

Renal involvementRenal involvementRenal involvementRenal involvement

• Biopsy is mandatory

• Lupus nephritis-

• class I : minimal mesangial lupus nephritis, the mildest. patients may have a normal urinalysis and creatinine level. No treatment, good prognosis.

• class II : mesangial proliferative lupus nephritis ,25% of pSLE .patients may have microscopic hematuria or proteinuria. Mild disease.

• class III- Focal lupus nephritis, 41% of pSLE. Often presents with hematuria and proteinuria. May present with nephrotic syndrome, hypertension, and abnormal blood urea nitrogen and creatinine levels.

• class IV : Diffuse lupus nephritis. 65% of pSLE. Patients present with hematuria, proteinuria, hypertension, low C3 and C4 levels, and elevated anti-dsDNA levels. 50% of glomeruli have evidence of active proliferation.

• Class V: membranous lupus nephritis. 29% of pSLE. Nephrotic syndrome, may occur alone or in combination with other types of nephritis. Class V nephritis tends to have a better prognosis than class III and IV, but can be refractory to treatment.

• class VI: sclerosing lupus nephritis. Global sclerosis of more than 90% of glomeruli. End-stage kidney disease.

• 10% of children with proliferative nephritis progress to end-stage renal disease within 5 years

• Graft survival after transplant is 91% with a living related donor and 78% after cadaveric transplant

Neuropsychiatric involvementNeuropsychiatric involvementNeuropsychiatric involvementNeuropsychiatric involvement

• 2/3 of pSLE.

• Often presents within the first year of diagnosis.

• 2nd leading cause of morbidity and mortality.

• Most frequent-headache.

• Other- decreased concentration, cognitive dysfunction, psychosis, seizures, transverse myelitis, central nervous system vasculitis, stroke. a. a. a. a. 26-year-old woman with SLE, positive for antiphospholipid antibodies who had acute ischaemic stroke.

She presented with right hemiparesis, and MRI revealed an infarct in the hind limb of the left internal capsule.

b 17-year-old woman with SLE and CNS vasculitis. She presented with status epilepticus.

MRI revealed multiple bilateral white matter lesions and diffuse angiogenic oedema, suggesting acute vasculitis.

c 35-year-old woman with SLE. She presented with reduced muscle strength and sensibility in the right half of her body.

MRI revealed a small intramedullary demyelinating lesion in the spinal cord suggesting acute myelitis

Hematologic involvementHematologic involvementHematologic involvementHematologic involvement

• >60% of pSLE will have cytopenia

• Leukopenia in 2/3, usually lymphopenia

• Anemia- Coombs-positive hemolytic anemia, Anemia of chronic disease

• Thrombocytopenia in up to 30% of patients.

• Antiphospholipid antibody syndrome-APS

• Laboratory abnormalities include a positive LAC, anticardiolipin antibodies, anti beta2-glycoproteinantibodies, prolonged PTT.

• Manifestations -thrombocytopenia, arterial or venous thrombosis, stroke, transient ischemic attack, chorea, recurrent fetal loss, avascular necrosis.

• Increased risk for Hodgkin’s and non-Hodgkin’s lymphoma, leukaemia.

Pulmonary involvementPulmonary involvementPulmonary involvementPulmonary involvement

• Pleuritis, pleural effusion, pneumonitis, pulmonary hemorrhage, pulmonary hypertension.

• Pleuritis most common- dyspnea and sharp, stabbing chest pain during inspiration.

• Pulmonary function may be abnormal with a restrictive defect and decreased diffusion capacity.

• Radiographs may demonstrate interstitial infiltrates, pleural thickening, and elevated hemi-diaphragms.

• Shrinking lung syndrome results from an impairment of the diaphragm secondary to pleural thickening and fibrosis.

Cardiac involvementCardiac involvementCardiac involvementCardiac involvement

• Pericarditis- the most common cardiac complication in pSLE. Anterior chest pain and dyspnea that is exacerbated by lying flat

• Higher risk for premature atherosclerosis especially with Increased BMI, male gender, increased creatinine clearance, elevated lipoprotein(a) levels, increasing age, weight-adjusted prednisone dose, and azathioprine

• Libman-Sacks endocarditis- Lupus valvulitis may predispose patients undergoing dental procedures to bacterial endocarditis.

• Myocarditis, bacterial endocarditis.

Gastrointestinal involvementGastrointestinal involvementGastrointestinal involvementGastrointestinal involvement

• In 1/3 of pSLE

• Serositis, vasculitis, pancreatitis, enteritis, acalculous cholecystitis.

• Vasculitis- risk for bowel perforation.

• Pancreatitis may be caused by active SLE, infection, corticosteroid use.

• Functional asplenia-risk for sepsis from Streptococcus pneumoniae and other encapsulated bacteria.

Endocrine involvementEndocrine involvementEndocrine involvementEndocrine involvement

• Hypothyroidism is very common in SLE.

• Rarely- Hyperthyroidism

• Diabetes mellitus may develop-> corticosteroid + obesity.

• Growth failure- 15%

• Delayed puberty- 11%

• Estrogen containing oral contraceptive agents is not recommended

Laboratory evaluationLaboratory evaluationLaboratory evaluationLaboratory evaluation

Has two important roles: to aid in diagnosis and to monitor disease activity

• CBC- cytopenias

• SMAC- elevated Cr, transaminitis, hypoalbuminemia

• Elevated ESR

• CRP can remain normal in pSLE; can be elevated during active infection

• A urinalysis- proteinuria, hematuria, casts

• Autoantibodies

• C3, C4- low or undetectable when active disease.

• Hypergammaglobulinema

• Positive Coombs

AutoantibodiesAutoantibodiesAutoantibodiesAutoantibodies

• ANA:• in 99% of patients with SLE.

• May be positive in up to 1/3 of the healthy population and in family members of patients

with SLE.

• ANA is not useful to monitor disease activity.

• Anti-dsDNA:• very specific for SLE

• in >75% of patients with pSLE.

• Helps in monitoring disease activity

• Anti-Smith antibody:• is highly specific for SLE

• in up to 50% of patients

• Not useful in monitoring disease activity.

• Anti-RNP antibody:• may be found in classic SLE, but often indicates mixed connective tissue disease

• Anti-SS-A (anti-Ro) and SS-B (anti-La) can be found in SLE

TreatmentTreatmentTreatmentTreatment

• Aim: reducing disease activity while preventing long-term toxicities.

• Most patients will require glucocorticoids and often immunosuppressive drugs.

GlucocorticoidsGlucocorticoidsGlucocorticoidsGlucocorticoids

• Glucocorticoids are the mainstay of pharmacological treatment.

• Oral prednisone, prednisolone, or IV high-dose methylprednisolone.

• Daily doses range from 0.5 to 2 mg/kg/day.

• The initial dose is decided by the extent of disease severity and organ involvement.

• Taper of glucocorticoid doses is usually based on improvement in disease activity,

including laboratory parameters.

• IVMP 30 mg/kg to a max of 1 g for 1–5 consecutive days is usually initiated at diagnosis. IVMP helps decrease the IFN signature of disease activity in lupus

• Follow: height and weight, healthy diet, low in salt, adequate calcium and vitamin D intake, annual eye exam for cataract and glaucoma

Hydroxychloroquine/ Hydroxychloroquine/ Hydroxychloroquine/ Hydroxychloroquine/ PlaquenilPlaquenilPlaquenilPlaquenil

• Antimalarial agent should be given to all patients with aSLE or pSLE.

• Hydroxychloroquine inhibits Toll-like receptor pathways and minimizes flare, treats skin disease, and decreases the rate of autoantibody production.

• Hydroxychloroquine has an important role in cardiovascular protection: anti-platelet, anti-thrombotic, lipid-regulating, anti-hypertensive, hypoglycemic properties,

• Ophthalmological screening for hydroxychloroquine induced retinopathy, which can present insidiously with subtle color vision changes and paracentral scotoma, making early detection difficult.

Mycophenolate Mycophenolate Mycophenolate Mycophenolate mofetilmofetilmofetilmofetil/ / / / CellceptCellceptCellceptCellcept

• In lupus nephritis has equivalent or better results than cyclophosphamide with lower rates of adverse effects, particularly infections.

• MMF can also be used as a steroid sparing agent in dermatological manifestations of SLE.

• Side effects: mild gastrointestinal symptoms, cytopenias, and teratogenicity.

Cyclophosphamide/ CytoxanCyclophosphamide/ CytoxanCyclophosphamide/ CytoxanCyclophosphamide/ Cytoxan

• For severe SLE, including lupus nephritis, life-threatening organ involvement, and neuropsychiatric manifestations.

• Given every 4 weeks for 6 months or Eurolupus protocol 500 mg every 2 weeks for six doses.

• Risk of infertility and premature ovarian failure- dose-duration-age-dependent.

• Increased infections. Eurolupus significantly lower adverse effects including infections.

• Increased risk of bladder cancer, dose-dependent.

Azathioprine/ ImuranAzathioprine/ ImuranAzathioprine/ ImuranAzathioprine/ Imuran

• Azathioprine for lupus nephritis, dermatologic and hematologic manifestations of pSLE.

• Increased risk of cancers- skin cancers and lymphomas

• Neutropenia, lymphopenia, and deranged liver function.

Rituximab/ Rituximab/ Rituximab/ Rituximab/ MabtheraMabtheraMabtheraMabthera

• Anti-CD20 monoclonal antibody, targets B-cells

• Approved by FDA for RA in 2006 and has been used off-label in the treatment of SLE patients with refractory disease

• Effective in treating SLE-associated cytopenias.

• Two phase III randomized controlled trials for moderate to severe lupus (EXPLORER) and for class III or IV lupus nephritis (LUNAR) did not meet their primary end points of significant reduction of disease activity compared to placebo

• In severe SLE organ involvement, benefit has been shown in using rituximab and cyclophosphamide together.

• Prior to rituximab: CBC with flow cytometry, quantitative immunoglobulins.

• Increased risk of infections.

• Patients may require IVIG replacement therapy for hypogammaglobulinemia

BelimumabBelimumabBelimumabBelimumab

• Human IgG1 monoclonal antibody to soluble BAFF

• Increased BAFF levels are associated with greater disease activity in SLE

• Approved in the USA and Europe in 2011 for the treatment of aSLE. Current trials in pSLE.

• Belimumab effective for moderately active disease with predominantly

mucocutaneous and/or musculoskeletal symptoms.

Potential future treatmentsPotential future treatmentsPotential future treatmentsPotential future treatments

• Rapamycin:• mTOR blockade

• Rapamycin blocks T cell activation in patients with SLE

• Anti IFN-regulated genes.• Ongoing trials -Sifalimumab, Rontalizumab, AGS-009, Vaccination against IFN-a, Blocking

activation of TLR7 and TLR9,

Long term outcomeLong term outcomeLong term outcomeLong term outcome

• Mortality rates in lupus has decreased significantly with 10 and 15 years survival exceeding 85%

• Median age of pSLE onset around 12 years, approximately 15% of pSLE patients would die by 22–27 years of age

• Early mortality d/t disease-related complications or infections

• Delayed mortality d/t severe lupus flare, end stage renal disease or cardiovascular disease.

• Morbidity d/t adverse effects of therapy and chronic inflammation:• Premature atherosclerosis with 50-fold increased risk for MI in 3rd,4th decades of life

• Osteopenia, osteoporosis and fragility fractures

• Avascular necrosis of hip

• Recurrent infections secondary to immunosuppressive medications.

• Increased risk of malignancy, particularly lymphoma

SLE in adolescentsSLE in adolescentsSLE in adolescentsSLE in adolescents

• Already challenging period in life

• Disease related effects- alopecia, malar rash, photosensitivity, cognitive dysfunction..

• Therapy related effects-hirsutism, moon faces, buffalo hump, acne, striae, weight gain, mucositis, alopecia infertility risk..

• Accepting the diagnosis of a new serious and chronic disease

• Family relationships, peers relationships.

• Noncompliance with medications and medical follow up.

• Special support, both from parents as well as treating physicians, can help them to cope with the disease and improve their long-term outcomes

Role of the PediatricianRole of the PediatricianRole of the PediatricianRole of the Pediatrician

• Hypertension screening in every visit

• Up to date on vaccinations.

• In case of fever- thorough evaluation and antibiotics if needed.

• Care should be given to try to avoid sulfonamides because their use can result in a disease flare.

• Team approach: the rheumatologist, primary care physician, ophthalmologist, nephrologist, and social worker.

• Discuss regularly- Medication compliance, healthy diet and exercise, follow-up with the various subspecialists.

• Sun protection year round with a sun protection factor >30 to try to prevent development of rash and systemic disease flare

VaccinationsVaccinationsVaccinationsVaccinations

• Although Vaccine-induced immune responses are variable, vaccine-related immunogenicity is generally adequate.

• All killed and recombinant vaccinations are safe and should be administered according to the recommended schedule.

• Vaccination against capsulated organisms like Pneumococcus, Hemophilus influenza and meningococci are recommended.

• All live attenuated vaccines (MMR, OPV) are contraindicated in pSLE patients receiving high-dose systemic immunosuppressive agents (including corticosteroids > 2 mg/ kg/day or > 20 mg/day for more than 2 weeks, steroid sparing medications and biologics) and for 3 months after these drugs are discontinued.

• Children who have neither received varicella vaccine nor had chicken pox in childhood should be given this live vaccine 4 weeks prior to start of immunosuppression

In RA and SLE patients there is a 1.5 times higher risk of high-grade cervical dysplasia or cervical cancer

compared with the general population

• The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by IBD, JIA and SLE

Conclusions:

Drug induced lupusDrug induced lupusDrug induced lupusDrug induced lupus

• First report 1945 by Hoffman: a 19-year-old army recruit who developed cutaneous, haematological and renal disease after treatment with sulfadiazine.

• 10–15% of patients diagnosed with SLE are drug induced

• Many drugs can induce autoantibodies, only a minority will cause clinical features of SLE

• Over 90 drugs were reported to cause DIL

• Classic medications- minocycline, procainimide, hydralazine, penicillamine, isoniazid, quinidine, phenytoin, and carbamazepine

• Minocycline-induced lupus usually seen in adolescent girls, usually with chronic use

Drug induced lupusDrug induced lupusDrug induced lupusDrug induced lupus

• M=F

• Presentation- constitutional symptoms, photosensitive rash, arthralgia, myalgia, and serositis. Subacute cutaneous lupus.

• Anti-histone antibodies in 95% of patients with DIL

• ANCA may be positive

• Treatment- discontinuing of the offending agent. A trial of NSAIDs, hydroxychloroquine, and corticosteroids may be needed.

• Symptoms usually abate within weeks to months of stopping the medication

• In some patients DIL will evolve into true SLE.

Diagnosis of DILDiagnosis of DILDiagnosis of DILDiagnosis of DIL

1.Exposure to suspected drug for at least 1 month

2.Symptoms such as arthralgia, myalgia, fever, serositis, rash

3.Positive ANA and anti-histone with negative specific antibodies anti-dsDNA, anti-smith, ENA

4.No previous evidence of SLE

5.Improvement of symptoms within days or weeks of drug discontinuation

DIL prognosisDIL prognosisDIL prognosisDIL prognosis

• Complete symptom resolution occurs within days or weeks

• Antibodies take longer to normalize.

• One death reported in the literature.

• If symptoms persist, the diagnosis should be reconsidered

Neonatal lupusNeonatal lupusNeonatal lupusNeonatal lupus

• In 1% of infants who had transplacental passage of maternal SSA or SSB antibodies.

• Common manifestations- rash, cytopenias, hepatitis with hepatomegaly.

• Most severe – 3rd degree heart block

• Except for the heart block, all other manifestations will resolve without intervention, usually within 6 months

Cutaneous Neonatal lupusCutaneous Neonatal lupusCutaneous Neonatal lupusCutaneous Neonatal lupus

• in 15–25% of children with NLE

• Often photosensitive but may be present at birth or in non-sun

exposed areas

• Resemble the rash of subacute cutaneous lupus erythematosus

(SCLE) or annular erythema

• Most frequently around the eyes

• Mostly between 4 and 6 weeks of age but may be present at birth

• The mean duration of the rash is 15–17 weeks

• >95% of mothers have anti-Ro

• Treatment - usually heals without treatment, corticosteroids may

hasten its resolution.

• scars or telangectasiae develop in 10–20% of children

Neonatal lupusNeonatal lupusNeonatal lupusNeonatal lupus

• Liver disease:

• 15-25% of NLE

• Asymptomatic elevated liver function tests- elevated transaminases, cholestasis

• Mild hepatomegaly

• Usually resolves in few months

• Hematologic disease:

• Most commomly thrombocytopenia in 1st week of life

• Resolves by 2- 4 weeks

• Neutropenia

• More rarely- haemolytic anemia, pancytopenia

• Neurologic disease:

• 8% hydrocephalus

Neonatal lupusNeonatal lupusNeonatal lupusNeonatal lupus---- cardiaccardiaccardiaccardiac

• Congenital heart block 1:15,000-20,000 life births

• 60-90% are due to maternal anti-Ro/ anti-la antibodies

• In up to 30% of infants born with NLE

• Fetal bradycardia is the first sign

• Fetal echo evaluated at 16 weeks’ gestation and at continuing intervals throughout pregnancy.

• When a fetus is identified as having heart block mothers are started on dexamethasone

• Nonreversible damage

• 30% -50% of infants with congenital heart block will require pacemaker implantation.

• Unlikely that they will develop SLE.

• Questions?