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Q. What is SLE ?
Ans: It is a multisystem disease characterized by the association of immunological abnormalities with pathological
changes affecting multiple organ systems particularly the skin, joints and vasculature.
(B) INDUCTION PHASE: It is C/B the appearance of autoreactive T cells that exhibit the loss of self-tolerence.
Mechanisms involved are
Failure of central thymic or peripheral tolerance mechanism.
Aberrant expression of HLA-DR molecule
Molecular mimicry induced by infection
Presentation of cryptic peptides during apoptosis.
(C) EXPANSION OF AUTOIMMUNE PROCESS: During this phase, autoantibodies are produced by population of
clonally expanded B cells which are directed against a limited number of nuclear and cytoplasmic antigens. 3
major targets are ------
Nucleosome ( anti-DNA & anti-histone)
Spliceosome ( anti-Sm & anti –RNP antibodies)
Ro and La molecules (anti-Ro and anti-La).
These autoantigens are clustered in distinct structures at the surface of apoptotic cells. Once the immune
tolerance to the intact particles is broken down, the autoantibody response diversifies to include more and more
components of the complex. This phenomenon is called EPITOPE SPREADING.
(E) IMMUNOLOGIC INJURY: The auto antibodies cause tissue injury by the following means :
Direct cell death
Opsonisation
Blocking of target molecule function
ADCC
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IMMUNE COMPLEX DEPOSITION AND COMPLEMENT MEDIATED LYSIS.
criteria defination
1. MALAR RASH It is a fixed erythema, flat or raised over the malar area tending
( 50%) to spare the nasolabial folds.
6. serositis a. pleuritis :
pleritic pain complained by patient
rub heard by physician
pleural effusion in X-ray or clinical finding
b. pericarditis:
rub heard by the physician
evidence of effusion
ECG.
Sometimes large masses of nuclear material are found extracellularly and these are surrounded
by leucocytes forming ROSETTES.
LE cell is present in 80% cases of SLE. If LE cells are present in large numbers, it suggests SLE.
Clinically the most commonly used method to detect ANA is INDIRECT IMMUNOFLOURESCENCE. THE PATTERN
OF NUCLEAR FLOURESCENCE SUGGESTS THE TYPE OF ANTIBODY PRESENT IN THE PATEINTS SERUM. 4 BASIC
PATTERNS ARE RECOGNISED -------
HOMOGENOUS or diffuse nuclear staining: Reflects antibodies to CHROMATIN, HISTONES and occasionally
DOUBLE STRANDED DNA.
RIM or peripheral pattern: Reflects antibodies to double stranded DNA. Specific for SLE.
SPECKLED PATTERN refers to the presence of uniform or variable sized speckles. It reflects the presence of
antibodies to non-DNA nuclear constituents. These components are easily extractable with buffered salt
solution and hence they are called EXTRACTABLE NUCLEAR ANTIGEN. Examples of ENAs are Sm antigen,
RNP, and SS-A and SS-B reactive antigens. THIS IS ONE OF THE MOST COMMONLY OBSERVED PATTERNS OF
FLOURESCENCE AND THEREFORE THE LEAST SPECIFIC.
Anti-Sm, Anti- U1RNP, Anti- SS-A, Anti- SS-B, Anti- topoisomerase 1 (Scl-70) ----- fine
speckled.
Anti-centromere: CREST syndrome.
NUCLEOLAR PATTERN: refers to the presence of few discrete spots of fluorescence within the nucleus and
represents antibodies to nucleolar RNA. Anti- U3RNP, Anti- PmScl, Anti- RNA polymerase.
Q. How many patients are ANA negative and how do they present?
Ans: 5-10 % patients are ANA negative but anti cytoplasmic antibodies positive i.e.
60% have anti- Ro
30% have anti-La
25% have anti- ss DNA.
THEY HAVE MANY SIMILARITIES LIKE SCLE like they have prominent malar rash, oral ulcers, photosensitivity
and SCLE like skin lesions. Systemic manifestations of SLE are rare.
Anti- Sm (30%): SPECIFIC FOR SLE. Sm is a protein complexed to species of small nuclear RNA.
A/W renal, CNS disease and vasculitis.
Anti- Ro (30%): It is a protein complexed to y1-y5 RNA. A/W increased photosensitivity, renal disease,
neonatal LE, Sjogren’s syndrome, SCLE.
Anti- histone (70%): Low incidence of renal and CNS disease. IT IS PRESENT IN 95% CASES OF DRUG
INDUCED SLE.
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Anti – ribosomal P (20%): A/W CNS lupus. The antigen is ribosomal P protein.
Antineuronal antibody (60%): A/W diffuse CNS lupus. The antigen is present in the neuronal
surface.
Anti – phospholipids antibody (50%): Thrombosis, Thrombocytopenia and Recurrent fetal loss.
The antibody is an acquired immunoglobulin (IgG/IgM). Since phospholipids are needed for normal
clotting process, these antibodies interfere with the normal clotting process. Hence they are also called as LUPUS
ANTICOAGULANT. It is identified in vitro clotting tests like prolonged APTT and kaolin clotting time
which is not corrected by normal plasma . Also by Russel Viper venom test.
Q. What are the poor prognostic factors in SLE ? 50% mortality in 10 years.
Ans:
(A) Serious renal involvement in the form of
High serum creatinine ( > 1.4 mg/dl)
Nephrotic syndrome ( 24 hr urinary protein > 2.6 gm)
Hypertension
(B) Serious CNS involvement
(C) Anemia. Thrombocytopenia
(D) Hypocomplementemia suggesting hightened disease activity
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(E) Antiphospholipid syndrome
(F) Low socio economic status
Leading causes of death in the 1st decade = INFECTION and RENAL FAILURE.
Leading causes of death in the 2nd decade = THROMBOEMBOLIC EVENTS.
In less than 10% cases permanent detoriaration of renal function can occur.
IN ALL PATIENTS , THERE IS A HIGHER RISK OF
CHILDHOOD ELDERLY
Earliest age of onset is 3 months Increased incidence of lung disease
The clinical picture, course and and Sjogren’s syndrome and lower
treatment are similar to the disorder in incidence of CNS disease and
the adults but CHILDREN USUALLY mesenteric vasculitis.
HAVE A MORE SEVERE DISEASE. Anti-Ro and Anti- La are frequent.
Liver and lymph nodes are most Association with HLA – DR3.
commonly enlarged.
CNS & KIDNEY may be involved.
These antibodies are not specific for NLE but are also seen in
Sjogren’s syndrome
SCLE
Normal population (0.5-2%).
Approximately half of NLE patients manifest skin lesions which may be present at birth or occur in the first
few weeks of life. The most common finding is an ERYTHEMATOUS SLIGHTLY SCALY ERUPTION ON THE FACE AND
PERIORBITAL SKIN (raccoon sign/ owl-eye/ eye-mask) with the SCALP, TRUNK, EXTREMITIES, NECK AND
INTERTRIGINOUS AREAS involved in the decreasing order of frequency. The eruption can be exacerbated by UV
exposure and PHOTOTHERAPY. The rash improves by 4-6 months of life and has usually completely resolved
without scarring BY 12 MONTHS.
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COMPLETE HEART BLOCK occurs due to fibrosis of the conducting tissue of the heart. There may be
associated pericardial and pleural effusion, ascitis, cardiomyopathy, and IUGR and hydrops fetalis.
Treatment:
1. sun avoidance
2. topical steroid
3. pacing
Prognosis : some children can develop SLE in later life and some mothers can develop CTD in later life.
(C ) CHRONIC CUTANEOUS LE ( CCLE) : DLE lesions occur in SLE patients. In 10% they are the presenting
lesion and in 33% they occur during the course of the disease.
Classic discoid LE
Hypertrophic / verrucous LE
LUPUS PROFUNDUS
Mucosal LE
Lupus tumidus
Chilblain LE
Lichenoid DLE
Bullous DLE
Rosacea like DLE
Annular atrophic DLE
LE gyratum repens
Rowell’s syndrome
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(2) LE nonspecific skin lesions
(A) Cutaneous vascular diseases
(a) VASCULITIS
---- LEUCOCYTOCLASTIC (palpable purpura, urticarial vasculitis)
---- PERIARTERITIS NODOSA.
(b) VASCULOPATHY
----- Degos disease like lesions
----- Secondary atrophie blanche
(c ) PERIUNGUAL TELANGIECTASIA
(d) LIVEDO RETICULARIS---- COMMON IN PATIENTS WITH CNS LUPUS.
(e) THROMBOPHLEBITIS
(f) RAYNAUD’S DISEASE
(g) ERYTHROMELALGIA
(h) PURPURA ---- causes are : thrombocytopenia, cutaneous arteritis, steroid therapy.
(B) Non scarring alopecia : mostly in active stage ( 50% of patients with active stage have this). Hair
recovers once the disease becomes inactive but the lupus hair tends to persist longer.
Lupus hair: occurs in 30% patients. These are coarse, dry, brittle, broken off shortened unruly hair
especially on the frontal margin. They have slowed anagen growth. They usually persist longer.
Telogen effluvium
Alopecia areata.
(D ) Sclerodermatous skin changes in face and limbs although mat like telangiectasia are rare.
(F) Panniculitis
(G) Urticaria
(O) Occlusion of large and medium sized arteries also occur suddenly---- may need amputation of the limb.
IMMUNOFLOURESCENCE shows the linear deposition of IgA, G, M , C3 at DEJ ( unlike DH but like BP).
However electron microscopy shows that the reactants are in the sublamina densa and not in the lamina lucida as
in BP.
Bulla predominantly occur in the face, neck and upper trunk but maybe widespread. Heal with scar and milia
formation. Also, photosensitivity +.
Treatment of choice is Dapsone alone or in combination with steroid. In resistant cases, thalidomide is used.
But anti- ds DNA and ENA are absent. Progression to SLE is rare.
FEATURES SLE RA
Deforming arthritis 25% Common
Sc nodules 5% 25%
X-Ray erosions rare Common
Kidney involvement common Rare
LE cell test 80% 15%
ANA 90% 20%
R-factor 40% 80%
Other musculoskeletal manifestations include --- myalgia, myositis, tendonitis, avascular necrosis of
bones.
CLASS IV: diffuse GN. : there is proteinuria, hematuria, RBC cast, nephrotic syndrome,renal insufficiency and
hypertension. IMMEDIATE TREATMENT SHOULD BE STARTED AT THIS STAGE OTHERWISE PROGRESS TO RENAL
FAILURE.
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CLASS V: diffuse membranous GN: severe proteinuria and nephritic syndrome.
CLASS VI: Advanced sclerosing GN: ESRD.
DEPOSITION IS MORE IN LESIONS MORE THAN 6 WEEKS, OVER SUN EXPOSED AREAS, UNTREATED
LESION.
Staining may be HOMOGENOUS ( chronic lesion), THREADY ( active lesion) or STIPPLED pattern ( in
uninvolved skin).
+ in half in nonexposed uninvolved skin of SLE. Presence of IgG suggests poorer prognosis.
Both fibrin and properdin have been demonstrated in the lesion of SLE --- PROPERDIN DEPOSITION IN
NORMAL SKIN CORRELATES WITH DISEASE ACTIVITY.
Deposits are also present in the blood vessels in skin lesions and uninvolved skin.
Epidermal nuclear deposits usually giving a speckled IgG pattern occurs in the basal cells of epidermis.
In DLE, deposits do not occur in the uninvolved skin. C1q is present in the deposits only in 29% of cases in
DLE (vs. 90% in SLE). These patients have greater risk of SLE.
Q. What are evidences for and against that DLE AND SLE are the same entity?
Ans.
(i) evidences in favour :
the cutanoeus lesions in both clinicohistologically are the same
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certain clinical features are present in both
Similar lab abnormalities are present in both though more common in SLE.
DLE patients occasionally go on to develop SLE
SLE patients develop DLE lesions
Conditions like LUPUS PANNICULITIS occur in both the two conditions.
(ii) evidences against:
The risk of patients of DLE developing SLE is very small. Higher in disseminated DLE ( 22%)
compared to localised DLE ( 1.2%).
This risk is not increased by various forms of stress, UVL, drugs chemicals etc.
DIF pattern is different.
Age and sex pattern is different
3 forbidden clones of lymphocytes synthesizing cellular autoantibodies develop in SLE BUT only one
develop in DLE.
Those patients ( HLA-B8 +) who convert from DLE to SLE and those with SLE who have discoid lesions
must be genetically predisposed to both the conditions.
CONCLUSION: PATIENTS OF DLE WITH HEMATOLOGICAL AND SEROLOGICAL ABNORMALITIES ARE NOT
CASES OF SLE IN DISGUISE BUT ARE CASES OF DLE , A SAPERATE ENTITY FROM SLE WITH DIFFERENT
GENETIC BACKGROUND.
Q. Define DLE ?
Ans. It is a relatively benign condition of the skin most frequently involving the face and characterized by
VARIOUS SIZED, USUALLY COIN SHAPED, ERYTHEMATOUS, WELL DEFINED SCALY PLAQUES WHICH TEND TO HEAL
WITH ATROPHY, SCARRING AND PIGMENTATION. THE SCALES ARE ADHERENT AND PLUG THE FOLLICULAR
ORIFICES.
There are hematological and serological changes in about half of the patients and these changes, with
other evidence, suggest an autoimmune etiology.
LOCALIZED DLE: The lesions are confined to the face above the chin.
DISSEMUNATED DLE: Lesions occur below the chin also. Hematological and serological abnormalities are more
frequently seen. More chance of developing SLE.
BASEMENT MENBRANE:
Thickening and tortousity in long standing cases.
PAS+, diastase resistant material is found not only in the DEJ but along the follicular dermal junctions as
well. These findings correlate with immunoreactant deposits.
Capillary walls show thickening, homogenization and increase in PAS staining intensity.
STROMA:
Predominantly lymphocytic infiltrate arranged along DEJ, around hair follicles and appendages
(with hydropic degeneration of basal cells).
By impinging on the pilosebaceous units, infiltrate causes gradual atrophy and disappearance.
Also dermis shows----- EDEMA, RBC extravasation and MELANOPHAGES, INTERSTITIAL MUCIN DEPOSITION.
SUMMARY: The salient features in the HPE of DLE is ( at least 2 must be present)
(A) Liquefaction degeneration of basal cell layer.
(B) Degenerative changes in the connective tissue characterized by hyalinization, edema and
fibrinoid change most marked immediately below the epidermis.
(C) A patchy dermal lymphocytic infiltrate with few plasma cells and histiocytes particularly
around the appendages.
(C) LE PROFUNDUS:
SUBCUTANEOUS TISSUE MAYBE INVOLVED WITH OR WITHOUT INFLAMMATION IN THE DERMIS AND
DEJ.
LOBULAR PANNICULITIS ---- fat necrosis is followed by fibrin deposition leads to hyalinization of
adipose lobules.
Stromal mucin deposition in well eshtablished cases.
Vascular changes like endothelial prominence, thrombosis, calcification and perivascular
fibrosis .
SCLE: It differs from SCLE in that the changes are most intense in the DEJ. They consist of -----
Less prominent hyperkeratosis and inflammatory infiltrate than discoid lesions
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Hydropic degeneration of basal cells sometimes severe enough to form clefts.
Colloid bodies ( common)
Dermal edema
Focal RBC extravasation and dermal fibrinoid deposits (common).
12. MUCOSAL DLE: 25% Mostly affects the oral mucosa as LP like lesions,erythematous
of DLE patients have patches with depressed centre, superficial ulcerations, lip
mucosal lesions. crusting, scar, leukoplakia and SCC.
Lower palpebral conjunctivitis, superficial punctuate keratitis,
Redness in the vulva and anus.
13. NAIL DLE Nail fold- erythema, telangiectasia,
clubbing, paronychia
Nails – red lunula, pitting,
leukonychia striata, onycholysis,
subungal hyperkeratosis.
14. LE telangiectoides: C/B persistent blotchy reticulate in the face, neck, ears, back
occurs in SLE & DLE. telangiectasia . Healing by of hands, breasts, heels and
punctuate atrophic scarring. sides of feet
Lesions mainly occur above waist and particularly around the neck, on the trunk and outer aspects of the
arms. The borders may show vesciculation and crusting. FOLLICLAR PLUGGING AND HYPERKERATOSIS are not
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prominent and the lesions resolve leaving grey white hypopigmentation and telangiectasias. The pigmentary
changes eventually resolve spontaneously.
TREATMENT OF SLE
1. GENERAL MEASURES ----
> Sun protection
> Bed rest during exacerbation
> Avoid secondary infection, mental and physical stress
> Correct anemia