Connective Tissue Diseases

Diana Jean D. Del Rio, M.D. F.P.D.S

Classification of Lupus Erythematosus Childhood DLE

I. Chronic Cutaneous LE Lack of female preponderance
A. Discoid LE Lower frequency of photosensitivity
B. Verrucous (hypertrophic) LE (Behicett 50% progress to SLE
C. LE-lichen planus overlap
D. Chilblain LE Immunoflourescence
E. Lupus Panniculitis (LE profundus) DIF (+) in >75% of cases
1. With discoid LE IG and complement at the DE junction in granular or
2. With systemic LE particulate pattern
II. Subacute cutaneous LE Early lesions (<8 weeks) may have (-) IF
A. Papulosquamous
B. Annular Differential Diagnosis:
C. Syndromes commonly exhibiting similar Differentiate from less morbid diseases
morphology Most definitive is do a biopsy
1. Neonatal LE o Seborrheic dermatitis
2. Complement deficiency syndromes o Rosacea
III. Acute cutaneous LE (SLE with skin lesions) localized o Lupus vulgaris
or generalized erythema or bullae o Sarcoid
o Drug eruptions
Discoid Lupus Erythematosus o Polymorphous light eruption

Usually confined to the Treatment:

skin There is no total cure for LE
Dull red or violaceous We cannot prevent lesions from appearing
Usually extend to the Avoid sunlight
hair follicles Use sunscreen
Range from 1cm to Avoid exposure to excessive cold, heat or trauma
larger and heals LOCAL: tropical corticosteroids Intralesional
spontaneously corticosteroids SYSTEMIC:
o hydroxychloroquine 6.5mg/kg/day
Localized DLE o if no response after 3 months
Usually localized above the neck o Chloroquine 250mg OD plus
Present periorbital edema and erythema some with o Quinacrine 100 mg OD
sever hyperkeratosis o Systemic corticosteroids
Scalp: scars are more sclerotic and depressed with Widespread or disfiguring lesions
scarring alopecia o Isotreinoin, dapsone, clofazimine,
Lips: grayish hyperketatotic patches eroded and etretinate, acitretin, interferon alfa-2a,
surrounded by an inflammatory zone oral gold and thalidomide
o Rituximab

Other forms of LE:

Verrucous (hypertrophic LE)

A LE lesion on scalp Atropic scar on the lesion
Generalized LE
Less commonly and usually superimposed on a
localized DLE case
Thorax and upper extremities are affected
Scalp may become bald and diffuse scarring on the
face and UE
Inc. ESR inc. ANA, leucopenia more common
Course of DLE:
95% of cases remain confined to the skin
Fever may signal progression to SLE
Patients with inc. ANA leucopenia, hematuria or
albuminuria are at risk
Spontaneous involution with scarring is common
Calcific nodules my develop in affected sites
Relapses common
BCC or SCC may occur in scars esp. lower lip
o Nonpruritic papulo-nodular lesions resembling
keratoacanthoma or hypertrophic lichen planus on
the arms and hands
LE-Lichen planus Overlap Syndrome
o Large, atrophic, hypopigmented, bluish-red
patches and plaques with telangiectasia and scaling
on the extensor surfaces of the extremities and
palmoplantar area
Chilblain LE
o A chronic unremitting form of LE with the
fingertips, rims of ears, calves and heels affected,
esp. in woman; due to cold
LE Paniculitis
o Deep and dermal subcutaneous nodules that are
rubbery-firm, sharply defined, and nontender
beneath the normal skin of the head, face, or upper
arms or chest, buttock and thighs
o Chronic and most commonly in women between
20 and 45

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Connective Tissue Diseases
Diana Jean D. Del Rio, M.D. F.P.D.S
Lupus Profundus
*Palpate to
appreciate the
lesion
Subacute Cutaneous LE
Scaly papules, which evolve either into psoriasiform
or polycyclic annular lesions
Scale is thin and detached and telangiectasia and
dyspigmentation
Follicles are not involved and no scarring
Occur on sun-exposed surfaces on the face and neck.
V-portion of te chest and back and upper outer arms
(shawl distribution)
Inner arms, axilla and flanks and knuckes are spared
Runs a mild course
Renal CNS or vascular complications are unusual
Erythematous patches, scaly
Treatment
Antimalarials
Low dose systemic __________
Photoprotection
Systemic Lupus Erythomatosus
American Rheumatism Association 11 criteria
1. Malar erythema
2. Discoid LE
3. Photosensitivity
4. Oral ulcer
5. Nonerosive arthritis
6. Serorsitis (pericarditis or pleurisy)
7. Nephropathy (albuminuria or cellular casts)
8. CNS disorder (unexplained seizures or psychosis)
9. Hematologic disorder hemolytic anemia with
reticulocytosis or leucopenia below 4000/mm3 on 2
occasions, or lymphopenia below 1500/mm3 on 2
occasions
10. Immunologic disorder: positive LE-cell
preparation, or antibody to ____ DNA or SM antigen,
or false (+) STS
11. ANA in abnormal titer unexplained
**4 out of 11 should be present
Cutaneous Manifestations:
Butterfly facial erythema: begins on the malar area
and bridge of the nose; may be associated with
edema; resolves without scarring
Bullous lesions on the sun-exposed areas; IgG, IgM,
IgA or C3 in granular or linear pattern of BMZ of DIF
Vascular lesions (50%): puffiness, erythema or
telangiectasia on the fingertips; red lunula; palms,
soles, elbows, knees and buttocks become
erythematous or purplish with overlaying scale;
petechia on the mouth
Lupus hairs:
o Broken off hairs in the frontal area as a
result of inc. fragility
Mucous membrane lesions (20-30%):
o Conjunctivitis, episcleritis, nasal and vaginal
ulcerations
o Oral mucosal hemorrhages, erosions and
ulcers
Multiple dematofibromas: >15
Leg ulcers:
o punched out, indolent with little
inflammation on the pretibial or malleolar areas;
caused by vasculitis or thrombosis due to
antiphospholipid antibodies
Rowell’s syndrome: EM-like lesions
Calcinosis cutis
Lupus Hair
*scalp smooth with a
patch of alopecia
Systemic Manifestations:
Earliest changes: arthralgia (95%)
Fever, weight loss, pleuritis, adenopathy and acute
abdominal pain
Thrombosis (due to lups anticoagulant),
thrombocytopenia, false (+) STS, livedo reticularis,
neurologic disorders and high risk of spontaneous
abortions
Renal: nephritic or nephritic
CV: myocarditis, pericarditis (the most frequent
cardiac manifestation) and endocarditis; Raynaud’s 
phenomenon (15%)
CNS: hemiparesis, convulsions, epilepsy, diplopia,
retinitis, choroidiis, psychosis and other personality
disorders; livedo reticularis (marker for patients at
risk for CNS lesions)
o Livedo reticularis is the mottling of
skin
Hematologic: ITP, Coombs (+) haemolytic anemia,
neutropenia and lymphopenia
GI: nausea, vomiting and diarrhea
Pulmonary: pleural effusions, interstitial lung disease
and acute lupus pneumonitis
Myopathy
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Connective Tissue Diseases
Diana Jean D. Del Rio, M.D. F.P.D.S
Etiology:
Sunlight precipitates SLE
Genetic:
o Prevalence in first-degree relatives in
1.5%
Sunlight:
o UV upregulates cytokines, causes release
or translocation of
sequestered antigens, and causes free
radical damage
Altered immune response:
o Reduce T- suppressor cell function
o Overproduction of gamma globulins by B
cells causes overresponsiveness to
endogenous antigens → immune complexes
→ tissue damage
o Externalization of cellular antigens, such
as Ro/SSA in response to sunlight → cellular
cytotoxicity
Drugs can precipitate SLE:
o Hydralazine
o Procainamide
o Sulfonamides
o Penicillin
o Anticonvulsants
o minocycline and INH
Laboratory findings:
Hemolytic anemia, thrombocytopenia, lymphopenia,
leucopenia
Increase ESR
Inc. IgG
Reversal of A:G ratio
Urinalysis: (+) albumin, rbc and casts
Immunologic findings:
ANA test: (+) in a third of all CT dis. and 95% or SLE;
hep-2 tumor cell line the most sensitive
LE cell test: specific but not very sensitive
dsDNA; specific, not very sensitive
anti-Sm antibody:20-30% sensitivity; highest
specificity for SLE
anti-nRNP; indicates low risk of renal disease and
good prognosis; seen in mixed CTD and SLE
anti-La antibodies:10-15% of SLE and 30% of
Sjogren’s syndrome
anti-Ro antibodies: 25% of SLE and 40% of
Sjogrens’s; frequently seen in SCLE (70%), neonatal
LE (95%), C2 and C4-deficient LE (50-75%), late-
onset-LE (75%) and Asian patients with LE (50-60%);
photosensitivity may be striking
serum complement: low levels indicate active
disease, often renal
Lupus band test: DIF; granular deposits along the DE
junction occur in 75% of lesions of DLE and SLE, in
normal skin in SLE
Anti-ssDNA antibody: sensitive but not specific;
many are phorosensitive
ANA patterns: peripheral, SLE but not specific; many
are photosensitive
ANA patterns: peripheral, SLE-specific (anti-DNA);
homogenous: not specific for SLE
Antiphospholipid antibody: anticardiolipin antibody
and lupus anticoagulant are subtypes; assocated
with a syndrome that includes venous thrombosis,
arterial thrombosis, spontaneous abortions and
thrombocytopenia
Treatment
Just to control the disease
Bed rest
Ibruprofen
Sunscreen and sun avoidance
Antimalarials
Corticosteroids- moderately severe cases; renal or
neurologic involvement; dosage is determined by
disease activity as measured by serum C3 level and
anti-dsDNA
o Methylprednisolone 1000 mg IV daily for
3 days, followed by oral prednisone 0.5-1mg/kg/day
Immunosuppressants: azathioprine, methotrexate
and cyclophosphamide
Rituximab
Dermatomyositis
An inflammatory myositis characterized by
prodromata, edema, dermatitis and muscular
inflammation and degeneration
Polymyositis:muscle involvement without skin
changes
Skin findings:
Begins with erythema and swelling of the face and
upper eyelids; eyelids become swollen and pinkish
violet (heliotrope), tender with minute telangiectasis
Erythematous urticarial papules and plaques on the
face and extremities; firm pitting edema on the
shoulder girdle, arms and neck
Atrophic, erythematous, scaly plaques on the scalp
Nails: periungual telangiectasia
Gottron’s Sign: reddish purple scaling eruption over
the knuckles, knees and elbows → pathognomonic
sign
Mechanic’s hands: hyperkeratosis, scaling, fissuring
and hyperpigmentation over the fingertips, sides of
thumb and fingers with occasional involvement of
the palms
Heliotrope Sign
Trunk is erythematous with scaly patches
Gottron’s papules Raynaud’s Phenomenon
Erythematous papules
Raynaud’s Phenomenon
Hypertrichosis
Regression of the disease → hyperpigmentations
with areas of hypopigmentation, atrophy and
telangiectasia
Calcium deposits in skin and muscles in more than
half of children with DM mostly on the upper half of
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Connective Tissue Diseases
Diana Jean D. Del Rio, M.D. F.P.D.S
the body around the shoulder girdle, elbows and
hands
Ulcerations and cellulitis
Muscle Changes
Proximal muscle weakness with acute swelling and
pain
Symmetrical weakness inv. Shoulder girdle, pelvic
region and sometimes the hands
Difficulty in swallowing, talking and breathing
Cardiac inv. With cardiac failure
Eruption of DM precedes muscle symptoms by
2-3 months
Amyopathic dermatomysitis or dermatomyositis sine
myositis
Absence of myositis with skin changes
Muscle inflammation may be present by
asymptomatic
Diagnostic Criteria:
Symmetrical weakness of the limb girdle muscles
and anterior flexors of the neck
Elevated muscle enzymes: CPK, transaminase, LDH,
aldolase
Abnormal EMG
Characteristic myositis on muscle biopsy
Typical dermatologic features
o 2 (plus dermatologic features) make
diagnosis probable; 3 definitive
Neoplasia with Dermatomyositis
th
More frequent in adults esp. in the 5th -6 decade
Ovarian cancer seen in more than 20% of women>
40 years old with DM
Childhood DM
2 variants:
1. Brusting type
o More common
o Slow course, progressive weakness, responsive to
steroids; calcinosis more common
2. Banker type
o Vasculitis of the muscles and GIT, rapid onset of
severe weakness, steroid responsiveness and death
Etiology of DM
Humoral immunity and vasculopathy mediated by
complement deposition is responsible for the muscle
findings of DM
Cell-mediated cytotoxicity causes muscle disease of
polymyositis
Viral infections (EBV)
Bovine collagen dermal implants
Laboratory Findings:
Increase creatine kinase, aldolase, LDH and
transaminases
Anemia with low serum iron, leucocytosis
In ESR
Muscle biopsy
X-ray studies with barium swallow: weak pharyngeal
muscles and collection of barium in the pyriform
sinuses and valleculae
EMG
Treatment:
Prednisone 60mg/day until severity decreases and
muscle enzymes almost normal, then taper slowly
with a treatment period of 25-36 months
Passive range of motion
Cyclosporine and IV immunoglobulin
Sunscreen with SPF >30
Antimalarials such as hydroxychloroquine 200-400
mg/day or 2-5mg/kg/day in children
Methrotrexate
Prognosis
Major causes of death:
o Cancer, ischemic heart disease and lung
disease
Risk factors
o Failure to induce clinical remissions, wbc
cound > 100,000 and temp. of 38C at
diagnosis, older age, shorter disease history
and dysphagia
Prognosis for children is considered guarded
Scleroderma
Sclerosis of the skin characterized by appearance of
circumscribed or diffuse, hard, smooth, ivory-
colored areas that are immobile upon the underlying
tissues and give the appearance of hide-bound skin
2 Types:
1. Systemic
a. Progressive Systemic sclerosis
b. Thiebierge-weisenbach syndrome or
CREST syndrome
2. Localized
a. Morphea- localized, guttate, generalized,
profunda and pansclerotic forms
b. Linear scleroderma (w/ or w/o melarheostosis or
hemiatrophy)
Morphea
Occurs more often in macules or plaques, or bands
and spots
Rose or violaceous macules appear → smooth, hard,
somewhat depressed, yellowish white or ivory-
colored lesions → margins are surrounded by a light
violaceous zone or telangiectases → elasticity is lost
Sites: trunk and extremities
Slowly involute over 3-year period
Early lesion areas involved are depressed and gradually
become white
Guttate Morphea- multiple, chalk-white, flat or
slightly depressed macules over the chest, back,
neck and shoulders which are not very firm
Generalized Morphea- widespread involvement
with indurated by hypo-or hyperpigmentated
plaques
Morphea profunda- sclerosis of dermis, panniculus,
fascia, muscle and bone
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Connective Tissue Diseases
Diana Jean D. Del Rio, M.D. F.P.D.S

Linear Scleroderma Acrosclerosis: inv. Of the hands and feet

Involving the arms or legs beginning in the first o Fingers become semi-flexed, immobile
decade of life and useless
May occur parasagitally on the frontal scalp and o Terminal phalanges are board-like and
exteneded partway down the forehead (en coup de indurated
sabre) o Round fingerpad sign
o Trophic ulcerations and gangrene may
Crest Syndrome occur on the tips of fingers and knuckles
May be limited to the hands (acrosclerosis) o Dilated, irregular nailfold capillary loop
associated with: present in 75%
C alcinosis Keloidllike nodules may develop on the
R aynaud’s phenomenon extremities and chest
E sophageal dysmotility o Pig skin-like with prominent hair follicle
with pigment around it
S clerodactylyl (always present)
Widespread diffuse calcification of the skin
T elangiectasia
Later, hyperpigmented spots of diffuse bronzing may
(+) anticentromere antibody in 50-90% of patients
be present
(highly specific for CREST)
The most characteristic pigment change is a loss of
Has the most favorable prognosis among the
pigment in large hairless patch with perifollicular
systemic type
pigmented pigmented retention within it

Internal Involvement:
Fibrosis, loss of smooth muscle of the internal
organs, and progressive loss of visceral function
The most frequent internal organ involved is the GI
tract, followed by the lungs, cardiovascular and renal
systems
Esophageal involvement (atony) is seen in >90%
→dysphagia and reflux esophagitis
Small intestinal atonia → constipation, malabsorption
or diarrhea
Pulmonary fibrosis → hypoxia, dyspnea and
productive cough
Progressive Systemic Sclerosis
Cardiac → dyspnea, palpitation, and symptoms of
A generalized disorder of connective tissue in which
congestive heart failure
there is fibrous thickening of the skin combined with
Death usually occurs from cardiac or renal failure
fibrosis and vascular abnormalities in certain internal
organs
Laboratory Findings:
Raynaud’s phenomenon is frequently the first
ANA is (+) in 90% with anti-nucleolar pattern the
manifestation and is nearly always present
most specific
Heart, lungs, GIT, kidney and other organs may be
True speckled or anti-centromere patterns is
involved
sensitive and specific for CREST
Woman affected 3 times more than men
Anti-single stranded DNA antibodies are common in
Peaks in the 65 and over age group
linear scleroderma
Dermatologic Manifestations:
Pathogenesis:
In the early phase, erythematous and swollen skin →
Primary vascular disease
skin becomes smooth, yellowish and shrinks so that
Autoimmune mechanisms
the underlying tissues are bound down
Microchimerism resulting in fetal antimaternal graft-
Earliest changes occur insidiously on the face and
vs-host reaction
hands
Borrelia afzelli and B. garnii in Europe and Japan
In the more advanced stages, these parts become
hidebound, so that the face becomes expression less
Treatment:
and the hands are clawlike (scierodactylia)
Give immunosuppressant to stop progression
Face appears drawn, stretches, and taunt with loss
In all varieties, treatment is unsatisfactory by
of lines of expression
spontaneous recovery may occur esp. in children
and the localized types
Daily exercise and physical therapy with full range of
motion
Regular massage, warmth, and protection from
trauma
Avoid exposure to cold and smoking
Vasospasm resulting in Raynaud’s phenomenon:
Difficulty opening the mouth with the lips becoming thin, Nifedipine 10mg QID, Dibenzylene 10mg TID,
contracted and radially furrowed Prazocin 1mg TID
Nose appears sharp and pinched Immunosupressives and corticosteroids
“neck sign”: ridging and tightening of the neck on
extension; (+) in 90%

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