Transcript Connective Tissue Diseases

Autoimmune connective
tissue disorders
 A connective tissue disease is any disease that has
the connective tissues of the body as a target of
pathology.
 Connective tissue is any type of biological tissue
with an extensive extracellular matrix that
supports, binds together, and protects organs.
These tissues form a framework, or matrix, for the
body, and are composed of two major structural
protein molecules: collagen and elastin.
 Many connective tissue diseases feature
abnormal immune system activity with
inflammation in tissues as a result of an
immune system that is directed against one's
own body tissues (autoimmunity).
 These are also referred to as systemic
autoimmune diseases.
 The autoimmune CTDs may have both
genetic and environmental causes. Genetic
factors may create a predisposition towards
developing these autoimmune diseases.
They are characterized as a group by the
presence of spontaneous overactivity of the
immune system that results in the
production of extra antibodies into the
circulation.
What Is Lupus?
 Lupus is a classic autoimmune disease whereby a
misdirected immune system leads to inflammation
and injury to one's own body tissues.
 Lupus erythematosus is a complex disorder
associated with numerous clinical signs and
symptoms and a wide range of laboratory
abnormalities.
 It shows a spectrum of varying prognosis, ranging
from a benign, solely cutaneous variant (localized
discoid) through to a potentially fatal systemic
illness
 Lupus can involve the skin, joints, and
internal organs. The heart, lungs, and
kidneys can also be affected in some
patients. There is no specific cure, but
treatments are effective at minimizing
damage and improving function.
Approximately 80% of lupus patients are
women.
Lupus erythematosus: subtypes
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Discoid lupus erythematosus (localized)
Discoid lupus erythematosus (generalized)
Verrucous lupus erythematosus
Subacute cutaneous lupus erythematosus
Systemic lupus erythematosus
Lupus erythematosus profundus
Lupus erythematosus–erythema multiforme syndrome
Drug-induced lupus erythematosus
Chilblain lupus erythematosus
C2 deficiency lupus erythematosus-like syndrome
Neonatal lupus erythematosus
Lupus Erythematosus
 Chronic Cutaneous LE
 DLE
 Verrucous LE
 Lichen Planus-LE overlap.
 Chiblain LE
 Lupus Panniculitis (LE profundus)
 With DLE
 With Systemic LE
Discoid LE
 Young adults. F:M=2:1
 Discoid lesions are characterized by discrete,
erythematous, slightly infiltrated plaques covered by
a well-formed adherent scale that extends into
dilated hair follicles (follicular plugging).
 Lesions heal centrally first with atrophy, scarring, and
dyspigmentation
 Up to 24% will have mucosal involvement.
 95% of cases confine to the skin at the onset and will
remain so.
 Follicular
plugging is
evident in this
patient with
discoid lupus
erythematosus
involving the
scalp.
 Discoid lupus erythematosus: close-up view showing
follicular plugging.
 By courtesy of the Institute ofDermatology, London,
Discoid LE
 Spontaneous involution with scarring is
common
 Progression to SLE is rare and may be
identified by abnormal labs.
 ANA – elevated
 Leukopenia, hematuria, or albuminuria
 skin inflammation (dermatitis) hair loss can be
temporary or permanent. Fortunately,
permanent hair loss is less common than
temporary hair thinning that recovers after a
disease flare.
Discoid lupus
of the scalp
 Discoid lupus affecting the scalp and face is shown. Note the
discoid plaques over eyebrows, forehead, and scalp, with
postinflammatory peripheral hyperpigmentation and central
scarring, resulting in alopecia.
Histology
 Thinned epidermis
 Loss of normal rete ridges
 Follicular plugging
 Hydropic changes of basal layer
 Lymphocytic perivascular infiltrate
 Increase mucin
 DIF is positive more than 75% of case with
Igs located at DEJ
Discoid lupus erythematosus: the
follicular epithelium shows basal
cell hydropic degeneration and
there is a heavy lymphocytic
infiltrate.
Discoid lupus
erythematosus: there is
marked follicular plugging
Treatment
 SUNSCREEN!!!!
 Topical steroid, high potency with occlusion if
needed
 Topical Tarcrolimos.
 Intralesional Injection with Kenalog
 Thalidomide
 Antimalarias: safest and most beneficial system
therapy.
 Plaquenil for 3 month, if no response switch to Aralen.
 If response is still incomplete, change to Quinacrine
Verrucous LE
 AKA hypertrophic LE
 Resembling KA or hypertrophic LP
 Treatment as DLE
SCLE
 Subacute cutaneous LE
 Annular
 Papulosquamous
 Syndromes commonly exhibiting similar
morphology
 Neonatal LE
 Complement deficiency syndromes
SCLE
 Psoriasiform, polycyclic annular lesions
 Shawl distribution: V neck, upper outer and inner
arms.
 ¾ of the patients have arthralgia,
 20% have leukopenia
 80% have positive ANA
 Associated with Ro/SSA and HLA-DR3-Positive.
 Hydrochlorothiazide can induce SCLE
Systemic LE
 Young to middle age women
 Skin involvement occur 80% of the case
 American Rheumatism Association has 11 criteria
 If 4 or more of the criteria are satisfied, the patient
is said to have SLE
ARA SLE criteria
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Malar Erythema
Discoid Lupus
Photosensitivity
Oral Ulcers
Arthritis
Serositis
Nephritis
Hematologic
CNS Changes
Immunologic
disorder
 ANA
Systemic Manifestation.
 Arthralgia is the earliest abnormality.
 95% of SLE patient will have arthralgia.
 Avascular necrosis of femoral head.
 Thrombosis in vessels secondary to
presence of lupus anticoagulant.
 Renal involvement in nephritic or nephrotic
type.
 Myocarditis, cardiomegaly, EKG changes.
Systemic Manifestation.
 CNS involvement
 Ideopathic thrombocytopenic purpura.
 Sjorgen’s syndrom
 Mixed with dermatomyositis
An erythematous, edematous eruption is present on the
malar area
 Multiple gangrenous lesions of the toes due to
necrotizing arteriolitis in a patient with systemic lupus
erythematosus and severe Raynaud's phenomenon.
Treatment of SLE
 Treatment of depending on the organ system(s)
involved.
 Skin, musculoskeletal, and serositis-type
manifestations generally respond to treatment with
hydroxychloroquine and nonsteroidal antiinflammatory medications.
 Porphyria cutaneous tarda may co-exist with LE, in
this case, Plaquenil is TOXIC!!!
 More serious organ involvement, such as CNS
involvement or renal disease, often necessitates
immunosuppression with high-dose steroids and
cyclophosphamide.
 Granular deposits of immunoglobulin G in the
basement membrane zone on direct
 immunofluorescence of lesional skin.
LE-LP Overlap syndrome
 Large atrophic hypopigmented bluish-red
patches and plaques.
 Response to treatment is poor
 Dapsone or Accutane maybe effective
Chilblain LE
 Chronic, unrelenting form of LE with
fingertips, rims of ear, calves and heels in
women.
 Chilblain lesions are due to cold
 Usual LE treatment
Lupus tumidus
 Round, erythematous
plaques on the upper arm.
the mucin stains with Alcian
blue
LE Panniculitis
 AKA LE Profundus
 Deep subcutaneous nodules 1-4cm
 Head, face, and upper arms
 Woman age 20-45
 Histology shows lymphocytic panniculitis, hyaline
degeneration of the fat, hyaline papillary bodies.
Over lying epidermis shows hydropic changes and
follicular plugging
 Treatment with Antimalarials.
Biopsy of a patient with lupus
profundus showing expansion of
the interstices of the fat lobule with
disintegrating leukocytes and
fibrin.
Neonatal LE
 Annular scaling erythematous macules and
plaques
 Appear on head and extremities
 First few months of life in babies born to
mothers with LE, RA, or other connective
tissue disease
 Resolve spontaneously by 6 month of age
 HALF of the patient has associated
congenital heart block, usually 3rd degree
Polymyositis/dermatomyositis
 Polymyositis is a rare inflammatory
disorder of muscle, the etiology of which is
unknown. If certain cutaneous lesions are
also present, the term ‘dermatomyositis’is
applied
Diagnostic criteria for
polymyositis/dermatomyositis
 Symmetrical weakness of proximal limb
muscles and anterior neck flexors
 plus esophageal and respiratory muscle
involvement
 Positive muscle biopsy features
 Elevated skeletal muscle enzymes
 Appropriate electromyographic features
 A typical rash
Either of these conditions may be confidently diagnosed if a patient
fulfills the first four criteria (polymyositis) or three of the four plus
the typical rash (dermatomyositis)
Variants of polymyositis
 Type Variant
I
Polymyositis
 II Dermatomyositis
 III Type I or II plus malignancy
 IV Childhood polymyositis or
dermatomyositis
 V Overlap syndromes
Dermatomyositis
 Gottron's papules - flat-topped violaceous papules
 Heliotrope - reddish -purple flush around the eyes
 Over knuckle streak erythema
 Shawl pattern
 Calcinosis Cutis may occur in oer half of the
children with DM
 Associated with Malignancy
Dermatomyositis
 Symmetrical muscle weakness
 assoc c malignant neoplasm when over 40
 periungual telangiectasia
 Prednisone 60mg until severity decrease.
Sunscreen, antimalarial
 Mechanics hand: hyperkeratosis, fissuring,
scaling involvement in the palm of the hand.
Muscle involvement
 Symmetrical muscle weakness
 Unable to raise arms to comb their hair
 Cardiac involvement with cardiac failure in
terminal phase
 Amyopathic dermatomyositis or
dermatomyositis sine myositis: DM without
muscle changes
there is atrophy with effacement of the ridge
pattern, basal cell hydropic degeneration
basal cell hydropic degeneration
 chronic inflammatory cell infiltrate
 Vacuolated, granular or fragmented
Scleroderma
 Scleroderma, also known as systemic
sclerosis, is a chronic systemic autoimmune
disease characterised by hardening (sclero)
of the skin (derma). In the more severe form,
it also affects internal organs
 These changes may affect the entire
extremity, face, neck, and trunk (thorax and
abdomen).
Localized Morphea
 Smooth, hard, somewhat depressed,
yellowish white, or ivory-colored lesions.
 Common on the trunk
 Margins surrounded by light violaceous
zone or by telangiectases.
 Slowly involute over a 3-5 year period.
Generalized Morphea
 Widespread hard indurated
plaque.
 No systemic involvement
 Resolution less likely than
the localized version.
Atrophoderma of Pasani and Pierini
 Reduction of thickness of derma connective
tissue
 Upperback and lumbar sacral area
 Benign course, usually resolve after few
months or few years.
 No effect treatment
 Variant of morphea.
Linear Scleroderma
 Linear lesions extend to length of arms or
leg
 Begin first decade of life
 May also occur parasagitally down the
forehead, known as en coup de sabre
 Parry-Romberg syndrome: progressive
facial hemiatrophy, epilepsy, exophalmos,
and alopecia, maybe a form of linear
scleroderma.
Progressive Systemic Sclerosis
is rapidly progressing and affects a large area of
the skin and one or more internal organs
Prognosis
 Skin involvement after 1 year of diagnosis:
 Group I – sclerodactyly alone – 71% 10
year survival rate
 Group II - Skin stiffness above metacarpalphalangeal joints but not involving trunk –
58% survival rate.
 Group III – truncal involvement – 21%
survival.
LAB Finding
 Topoisomerase I (formerly Scl–70) is
present in 20-30% of patients with diffuse
disease (absent in limited disease) and has
an increased association with pulmonary
fibrosis
 Anticentromere antibodies are present in
about 60-90% of patients with limited
disease and 10-15% with diffuse disease.
 Systemic sclerosis: early
stage showing
characteristic swollen,
sausage-shaped fingers
Systemic sclerosis: note the
flexion contractures. The skin
is bound down and
appears atrophic. There is
periungual erythema
Systemic sclerosis: the
fingertips are tapered
Systemic sclerosis:
(microstomia)there is
perioral scarring with
atrophy
 Systemic sclerosis: extensive telangiectasia
as seen in this patient is more often a feature
of the limited variant
Histology
 Increased collagen bundle and thickness of
the derma.
 Pilosebaceous units are absent. Eccrine
glands and ducts are compressed by
collagen.
 Eccrine glands present at the mid dermis
rather than at the junction of dermis/subQ
fat.
CREST Syndrome
 AKA Thibierge-Weissenbach Syndrome.
 Systemic sclerosis may be limited to the
hands, and is called acroslerosis.
 Not as severe as PSS
 ANA shows anticentromere antibody, and is
highly specific.
 Most favorable diagnosis
 Calcinosis (the deposition of calcium nodules in
the skin),
 Raynaud's phenomenon (exaggerated
vasoconstriction in the hands, with fingers
undergoing white-blue-red color transitions in the
cold),
 Esophageal dysfunction (leading to difficulty
swallowing),
 Sclerodactyly (skin thickening on the fingers), and
 Telangiectasias (dilated capillaries on the face,
hands and mucous membranes).
Eosinophilic Fasciitis
 Patient engaging in strenuous muscular
effort few days or week before acute onset
of weakness. Follow by severe induration
of the skin and subQ tissue of forearms and
legs.
 Coarse peau d’orange appearance.
 Groove sign: depression follow the course
of underlying vessles when arms are hold
laterally.
 Excellent response to corticosteroid.
Comparison of deep morphea and eosinophilic fasciitis. A Note the
‘pseudo-cellulite’ appearance of the involved skin of the thigh
in deep morphea. B In eosinophilic fasciitis, the level of
fibrosis is also deep.
Histology
 Patchy lymphocytic and plasma cell
infilrate in the fascia and subfacial muscle
and great thickening, 10-50 times normal of
the fascia.
Mixed Connective Tissue Disease
 As originally defined by Sharp et al., mixed
connective tissue disease (MCTD) represents
a clinical condition in which patients have an
overlap of signs and symptoms of systemic
sclerosis, systemic lupus erythematosus, and
polymyositis/dermatomyositis
 Clinical features include: arthralgias and
nondeforming arthritis, swollen hands with
tapered or sausage-shaped fingers, Raynaud's
phenomenon, abnormal esophageal
motility,myositis, lymphadenopathy, fever,
hepatomegaly, serositis, and splenomegaly
 In addition, their sera invariably contained
high titers of antibody to a saline extractable
nuclear antigen (ENA), U1-RNP, and
speckled antinuclear antibody
Sjogren’s Syndrome
 AKA Sicca syndrome
 Triad of keratoconjunctivitis sicca,
xerostomia, and rheumatoid arthritis.
 RF is usually positive
 Elevated C-reactive Protein, IgG, IgA, and
IgM
 80% has anti-Ro/SSA antibody.
 >50% have anti-La/SSB antobodies
 Only symptomatic treatment available.
The end
Rheumatoid Nodules
 20-30% of RA patients
 Subcutaneous nodules
 Found anywhere on the body
 Histologically shows dense foci of fibrinoid
necrosis surrounded by histiocytes in
palisaded arrangement.
Relapsing Polychondritis
 Intermittent episodes of inflammation of the
articular and nonarticular cartilage
eventualing in chondrolysis.
 MAGIC syndrome = Behcet’s + Relapsing
Polychondritis (Mouth And Genital ulcers
with Inflamed Cartilage)
 Treatment with Dapsone for few weeks,
then maintenance for 4-6 asymptomatic
months.