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Systemic Lupus ErythematosusSheelendra ShakyaDept. of Pediatrics, KMCTH

IntroductionA complex disorder of multifactorial origin resulting from interactions among genetic, hormonal and environmental factors acting in concert to cause activation of helper T cells and B cells that results in the secretion of several species of autoantibodies.

In this complex web, each factor may be necessary but not enough for the clinical expression of the disease; the relative importance of various factors may vary from individual to individual.

Topics of DiscussionPathogenesisClinical presentationDiagnosisUseful investigationsLupus nephritis TreatmentPrognosis

PathogenesisFundamental defect is a failure of the regulatory mechanisms that sustain self-tolerance.

Anti-bodies identified againstNuclear componentsCytoplasmic componentsCell surface antigens of blood elements incl. phospholipids

PathogenesisGenetic factorsHormonal InfluencesEnvironmental TriggersImmune Dysregulation

Pathogenesis

PathogenesisMost visceral lesions are mediated by immune complexes (Type III hypersensitivity)Autoantibodies against red cells, white cells and platelets mediate their effects via Type II hypersensitivity.In tissues, nuclei of damaged cells react with ANAs, lose their chromatin pattern, and become homogeneous, to produce LE bodies.

Case studySwastika Maharjan8yrs/F from BaneshworDOA: 065.1.3c/o puffiness of face, swelling of lower limbs, oral ulcer and skin rash, fever since 3 days.

Started e fever followed by facial puffiness and generalized body swelling 1 mth back. Diagnosed as AGN at Kanti and treated with antibiotics, diuretics and steroid. Discharged on improvement. On follow up, antibiotics changed, Urine albumin +++; Diuretics continued. After 12 days of stopping diuretics, swelling reappeared. Diagnosed as Nephrotic Syndrome e culture proven UTI. Treated with Ofloxacin.

HPIAfter 7 days of treatment with Oflo, child developed oral ulcers and skin rashes suspected to be drug rash and was switched to Cefixime. Was brought to KMC. Also h/o fever, multiple oral ulcers and skin rashes, more on face and few on the thigh, erythematous, macular, non itching e h/o decreased urine output. Occassional c/o joint pains. No h/o SOB, photosensitivity, burning micturition.

CRP >6mg/dl, Urine RME : RBC and pus plenty, albumin +TC8400cumm N82L17M1 Hb 13gm%ESR 52mm in 1st hr

O/EIll looking, oral ulcers, facial puffiness, malar rashPallor +, B/L pitting edema of lower limbsChest: dullness from 5th ics downwards on Rt. and 3rd ics downwards on Lt.; decreased B.S. on lt. inframammary regionCVS: S1+ S2+ M0P/A: umbilicus everted, mild distension, soft, non tender, no organomegaly, shifting dullness +, fluid thrill Pigmented rash on lateral aspect of rt. thigh

InvestigationsCBC:TC 3500 N63L36M1;Hb 6.9gm%; PLT 42000/cummESR 72mm in 1st hourPeripheral Smear: normocytic, normochromic to mildly hypochromic e mild anisocytosis. Plt reduced on smearBiochemistry:Urea 96mg/dl Cr 1.1mg/dl; Na 123meq/L, K 4meq/LTotal protein: 4.3g/dlAlbumin: 3.6g/dlTotal Cholesterol 210 mg/dlHDL: 27mg/dlTriglycerides: 697mg/dl LDL could not be calculated. ANA , CRP, ASO, RA factor- negativeUrine: pus 6-8/hpf, RBC plenty; Albumin 2 +, cast 0-224 hour urine volume: 350ml24 hour urinary protein 2717mg.Urine C/S- insignificant bacteriuriaMontoux test: no induration after 72 hrsReticulocytes: 4%Albumin repeated after 2 weeks: 1.8mg/dlAnti-dsDNA by ELISA- positive (69.12 IU/ml)

USG:B/L medicorenal diseaseB/L pleural effusionMinimal pericardial effusion.Ascites

CXR: B/L pleural effusion

Repeat Urine RMEs: persistent albumin, RBC and pus cells.

DiagnosisSLE with secondary Nephritic Syndrome with Culture proven UTI

Child was started on Steroid and diuretics. Antibiotics for UTI continued and she was closely monitored.

During the course of treatment, she got symptomatically better but ascites increased and her BP was also in a rising trend.

Due to parental wish and the need for specialist nephrologist expertise, she was referred to Kathmandu Nursing Home where she was continued with the same medication.

Clinical PresentationSkin manifestationsRenal diseaseNeuropsychiatric ArthritisCardiacRespiratoryHaematologyGastrointestinal

Muscles and bonesJoint/muscle pain, myositis, proximal myopathy.Any joint can be affected, but the most common spots are the hands, wrists, and knees. Usually the same joints on both sides of the body are affected. The pain can come and go, or it can be long lasting.Non-erosive polyarthritis with periarticular and tendon involvement.

Skin manifestationsButterfly rashAlopeciaOral ulcersPhotosensitivity

Skin manifestationsDiscoid lupusEars, cheeks, scalp, forehead, chest3 stage rash ErythemaPigmented hyperkeratotic oedematous papulesAtrophic depressed lesionsLivedo reticularis (net-like rash)Raynauds purpuraUrticariaConjunctivitisBullae

RenalProteinuriaCastsOedemaUraemiaAcute glomerulonephritis

Mesangial proliferative lupus nephritisAdvanced sclerosis lupus nephritisMembranous lupus nephritis

NeuropsychiatricCentral Nervous SystemHeadacheMood disorderCognitive dysfunctionSeizure disorderAcute confusional stateAnxiety disorderCerebrovascular diseasePsychosisMovement disorderDemyelinating syndromeAseptic meningitisMyelopathy

Peripheral Nervous SystemGBSAutonomic neuropathyMononeuropathyMyasthenia gravisCranial neuropathyPlexopathyPolyneuropathy

Neuropsychiatric syndromes in SLE as defined by American College of Rheumatology

RespiratoryPleuritis (+/-Pleural effusion)Acute pneumonitisChronic interstitial lung diseasePulmonary haemorrhagePulmonary OedemaShrinking Lung SyndromeRestrictive lung impairment with no respiratory symptoms

Cardiac

CardiacPericarditis (+/- effusion)MyocarditisCoronary Artery DiseaseLibman-Sacks endocarditisValvular insufficiencyCardiomegalyMyocardial perfusion defects - IHD

HematologicalThrombocytopeniaLeucopeniaLymphopeniaAnaemia due to chronic disease or secondary to Coombs positive haemolytic anaemiaINR, ESR increasedCRP normal, unless intercurrent infection.

GastrointestinalHepatosplenomegaly Nausea and vomiting

ConstitutionalFatigueFeverWeight lossLymphadenopathy

Diagnostic criteriaMalar rashDiscoid lupusPhotosensitivityOral or nasal ulcerationNon-erosive arthritisSerositisNephritisNeurologicalHaematologicalImmunologicalAnti-nuclear antibody

Fixed erythema, flat or raised, over malar eminences, tending to spare nasolabial foldsErythematous raised patches of adherent keratotic scaling and follicular plugging. Atrophic scarring may be seen in older lesions.Skin rash as a result of unusual reaction to sunlight (UV rays)Oral or nasopharyngeal ulcers, usually painless, observed by a physicianNon-erosive arthritis involving 2 or more peripheral joints, characterised by tenderness, swelling or effusionPleuritis pleuritic pain, rub heard or pleural effusion, or, Pericarditis documented by ECG or rub or pericardial effusionPersistent proteinuria > 0.5g/day not > 3+. Cellular casts: red cell, haemoglobin, granular, tubular or mixed.Seizures or psychosis in the absence of offending drugs or metabolic derangement.Haemolytic anaemia with reticulocytes, or: Leucopenia < 4000/mm3 on 2 or more occassions, or:Lymphopenia