SYSTEMIC LUPUS ERYTHROMATOSUS MANIFESTING AS NEPHROTIC SYNDROME

BY DR.TAMPHASANA WAIROKPAM,1Yr Resident

DEPT. OF INTERNAL MEDICINE,KVGMCH, SULLIA

• Herewith I am presenting an interesting case- 22 yrs old female patient ,married from Periyapattna, who was referred to us from Dermatology dept for e/o edema & facial puffiness .

• Her primary problem, which brought her to dermat. dept was facial rash of 1 yr duration, the rash used to aggravate & cause burning pain on exposure to sun- suggestive of photosensitivity- malar rash .

• However she did not had rashes over other sun exposed area.

• She developed Facial puffiness & edema of legs for 1 month, apparently more in the morning hours, but there was no oliguria or haematuria.

• On further enquiry she had chronic mild Intermittent ,on & off fever, headache, easy fatiguability , weight loss ,anorexia, recurrent oral ulcers, & alopecia.

• She had bilateral wrist and knee joint pains for last 1 year.

• She did not had similar problems prior to 1yr.• She was not on any regular medication & there was no

history of drug allergy .• She was on mixed diet , she had decreased appetite &

decreased sleep.• Her Bowel and bladder habits regular.• She attained menarche at 13 yrs , cycles regular(4/30)

&there was no h/o menstrual irregularity.• She is married & there was no h/o pregnancy loss• No similar complaints in the family

To summarise

• Young married lady with – Fever, Arthralgia, Malar rash, photosensitivity, & other constitutional symptoms for ~ 1 yr , now presenting with Edema & facial puffiness.

• D/D for Prolonged fever & constitutional symptoms– Infections

• SBE• TB

– CT Disease • SLE• RA• MCTD• Vasculitis

– Malignacy• Lymphoma• Chr Leukemia

• Edema & Facial puffiness on the background of prolonged illness– Renal

• Nephrotic syn• Immune mediated AGN• Renal failure

– Malabsorption– Severe Anemia & hypoprotenemia of chr. Disease

• In this patient we considered CT disease SLE – Arthralgia– Typical rash– Photosensitivity– Oral ulcers

• Complicated by– ? Nephrotic syndrome – ? Renal failure

General physical examination• General examination: • Patient is conscious, cooperative, comfortably sitting on bed, well

oriented to time, place & person.• Her BMI was 16.06• Her temp 100`F, • PR 98b/m, regular, normal volume, character , all peripheral pulses felt.• BP :170/100 mm Hg.• RR 16/min. • She was Pale & had Malar rash, Facial puffiness, periorbital edema &

b/l Pitting pedal edema .• There was no icterus, cyanosis, clubbing, lymphadenopathy or orogenital

ulcers .• Her Fundus showed grade 2 htn retinopathy.• There was no skeletal or joint deformity or e/o active arthritis.

Systemic examination• All systemic examinations were normal except

for a short systolic murmur in the mitral area.

• CVS: apex in the 5th ICS in the MCL ,S1,S2 heard, systolic murmur in the mitral area.

• P/A-soft ,no tenderness, no organomegaly, BS+.• CNS-NFND, plantars are b/l flexors.• RS- Clear VBS b/l

SUMMARY

• 22 yrs old lady with • Malar rash• facial puffiness & B/L Leg edema• Pallor• Hypertension & Gr II retinopathy• Systolic murmur at apex.

Investigations revealed :• Anemia(hb- 5.1 gm%)• Thrombocytopenia ( 70,000)• Leucopenia (2600)• ESR: 77 (raised)• 24 hrs urinary protein: 5.1 gm• Normal GFR• Hypoalbuminemia( S alb-: 2 gm/dl)• ANA : +• Anti ds DNA : +• Anti histones +• USG ABD/Pelvis – mild hepatosplenomegaly, & b/l mild

pleural effusion.• Other investigations were normal.

Diagnosis - SLE

• Young lady with Fever, Arthritis, Malar rash, Photosensitivity, oral ulcer

• Anemia, Thrombocytopenia, leukopenia• High ESR• Pleural effusion• + ANA & Ds DNA• Nephrotic proteinuria

• Management: • Inj. Methyl prednisolone 1g iv OD for 3 days.• followed by oral prednisolone 40 mg/day in

divided doses.• Diuretics, anti- hypertensives, hematinics &

blood transfusion.• At discharge, oral prednisolone 40 mg in

divided doses was advised to be tappered after 1 month over a peroid of 1 month.

• At discharge: Pt is comfortable, stable, edema & facial puffines had reduced markedly.

• P.R- 82 bpm.• B.P- 150/90mm hg

– Hb- 7.2 gm%– TLC- 4,400– DLC-N75,L 18, M 7– PLT – 92,000.

In view of development of renal involvement(NS) , pt was referred to higher centre for renal biopsy and further management with immunosuppressive drugs.

Review on SLE

• Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes.

• Ninety percent of patients are women of child-bearing years.

• Prevalence of SLE is 15–50 per 100,000.

DEFINITE FACTOR : Ultraviolet B lightPROBABLE FACTOR : Sex hormones; F:M ratio is 9:1 ; 3:1 in young and old.POSIBLE FACTOR :1)Dietary -high intake of saturated fats2)Infectious agent -Bilateral DNA human retroviruses, endotoxins, bacterial toxins.3)Medication –Hydralazine, Procainamide, INH, Hydantoins, Chlorpromazine, Methyldopa, d-penicillamine, minocycline, TNFα-antibodies.

Causes

Triggering agents

Abnormal immune regulation

T cells

B cells

Excessive cytokine release

Autoantibody formation

Immune complexes build up in the tissues and can cause inflammation, injury to tissues, and pain.

Criteria for diagnosis of lupus

S.N

Criteria Definition

1 Malar RashFixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

2Discoid Rash

Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions.

3Photosensitivity

Skin rash as a result of unusual reaction of sunlight.

4 Oral UlcersOral or Nasopharyngeal ulceration, usually painless.

5 ArthritisNonerosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion.

A person shall be said to have SLE if any 4 or more of the 11 criteria are present, serially or

simultaneously, during any interval of observation

S.N.

Criteria Definition

6 Serositis

a) Pleuritis –convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effision.

ORb) Pericaditis-documented by ECG or

rub or evidence of pericardial effusion.

7Renal Disorder

a) Persistent proteinuria greater than 0.5 gms. per day or greater than 3+ if quantitation not performed.

ORb) Cellular casts- may be red cell,

hemoglobin, granular, tubular, or mixed.

8Neurologic Disorder

a) Seizures –in the absence of offending drugs or

known metabolic derangements; e.g.-uremia, ketoacidosis, or electrolyte imbalance.

b) Psychosis –in the absence of offending drugs or known metabolic derangements; e.g.-uremia, ketoacidosis, or electrolyte imbalance.

9

Hematologic Disorder

a) Hemolytic Anemia –with reticulocytosisOR

b) Leukopenia –less than 4,000/mmOR

c) Lymphopenia –less than1,500/mmOR

d) Thrombocytopenia –less than 100,000/mm

in the absence of offending drugs

10

11

Immunologic Disorder

Antinuclear antibodies

Anti- dsDNA, Anti-Sm and/ or anti phospholipid

Abnormal titre of ANA at any point in time in the absence of drugs known to induce ANAs.

Lupus nephritis

• Proteinuria• Nephrotic syndrome• Granular casts• Red cell casts• Hematuria• Decreased renal function• HTN• ARF• Accelerated atherosclerosis, hyperlipidemia,

hyperglycemia.

Management

? NSAIDsHydroxychloroquine + steroid -5-10mg/dayMethotrexate 10-20mg/weekPersistent pain in one joint only- ischaemic necrosis of bone

1) Musculoskeletal

2) Cutaneous LupusProtective clothingSunscreen lotionLocal glucocorticoidsHydroxychloroquin 400mg/dayQuinacrine 100mg/dayEtiretinate 1mg/kg/day in divided dosesDapsone, Thalidomide Cytotoxic drugs

3) Serositis-• NSAIDs + Steroids 10-15mg/day

4) Aggressive TherapyManifestation usually responsive to high dose

glucocorticoids Vasculitis Severe dermatitis of SCLE or SLE Polyarthritis Polyserositis – Pericarditis, pleurisy, peritonitis Myocarditis Lupus pneumonitis Glomerulonephritis – proliferative forms Hemolytic anemia Thrombocytopenia Diffuse CNS syndrome – acute confusional state,

demyelinating syndromes, intractable headache, serious cognitive defects Myelopathies .Peripheral neuropathiesLupus crisis – high fever and prostration

Cytotoxic Drugs

Drug Initial Dose

Maint.Dose Advantage Adverse side

effectInci

.

Azathiopri--ne

requires 6-12 monthsto work Well

1-3mg/kg/

Day

1-2mg/kg/Day

Probably reducesflares, reduces renalscarring, reducesglucocorticoid doseRequirement

Bone marrowsuppression,LeukopeniaInfection (herps zoster),Malignancies,Infertility,Early

menopauseHepatic damageNausea

<5 

1510

<51510<515

Cyclophop-

-hamide

Requires 2-16 weeks towork well

1-3 mg/kg/day orally or 8-

20mg/

kg IV once a month +

mesna

0.5 mg/kg/DayOrally or 8-20mg/

kgIV Every4-12 Wk

+ Mesna

As for azathioprine probably effective in higher proportion of patient

Bone marrow suppression

<5

Azathio--prine

plus Cyclophpsp

o-mide

1.5-2.5 mg/kg/

day orally

1.5-2.5 mg/kg/

day orally

1-2 mg/kg/day Orally

1-2 mg/kg/day orally

Possibly moreeffective than one drug

Infections

Cystitis

40

15

Combination Therapy

Prognosis of SLE• Survival in patients with SLE in the United States, Canada,

Europe, and China is approximately 95% at 5 years, 90% at 10 years, and 78% at 20 years.

• In the United States, African Americans and Hispanic Americans have a worse prognosis than Caucasians, whereas Africans in Africa and Hispanic Americans with a Puerto Rican origin do not.

• Poor prognosis (~50% mortality in 10 years) in most series is associated with (at the time of diagnosis)– high serum creatinine levels [>124 mol/L (>1.4 mg/dL) hypertension– nephrotic syndrome (24-h urine protein excretion >2.6 g)– anemia [hemoglobin <124 g/L (<12.4 g/dL)]– hypoalbuminemia– hypocomplementemia – aPL

• This case is presented to showcase most of the common clinical manifestation of a rare disease.

THANK YOU