Autoimmune and Connective Tissue Disorders

Assist. Prof. Dr . Ali elethawi

Specialist dermatologist

C.A.B.D ,F .I .C.M.S

Autoimmune and Connective Tissue Disorders

A group of heterogeneous illnesses that have in common the development of

immunity to particles of self-DNA,

with

skin-only disease at one end of the spectrum and severe visceral involvement at the other.

Lupus erythematosusLupus erythematosus Lupus erythematosus (LE) range from the Lupus erythematosus (LE) range from the purely cutaneous type purely cutaneous type (discoid LE), through patterns associated(discoid LE), through patterns associated

with with some internal problems some internal problems (disseminated discoid LE and subacute cutaneous LE)(disseminated discoid LE and subacute cutaneous LE) , ,to a to a severe multisystem disease severe multisystem disease (systemic lupus erythematosus, SLE)(systemic lupus erythematosus, SLE)..

DLE DLE ( ( purely cutaneous) purely cutaneous) SCLESCLE (some internal problems)(some internal problems)

SLESLE (severe multisystem disease )(severe multisystem disease )

Causes of SLEI. Genetic factor

+ve FH in 5-13% of lupus patients complement deficiencycomplement deficiency

certain HLA typescertain HLA types . .All these increase susceptibilityAll these increase susceptibility ..

II. Environmental factors: 1.UV light, especially UVB, flares SLE in most patients

2 .Drug-induced lupus. Drug-induce lupus may resemble SLE both

clinically and serologically .eg; hydralazine, beta-blokers, isoniazid, penicillamine, procainamide .

3 . Infection. There has been continuing interest in the possibility that infectious agents might initiate or flare.

Causes of SLEIII. Sex hormones

female : Male= 9:1 The sex difference is most prominent during the female reproductive years.Its likely due to the effect of sex hormones on the immune system.

High levels of estrogen and progesterone promote humoral autoreactivity .

IV. Abnormal immune systemHyperactivity in B and T lymphocyte,

Autoantibodies to DNA, RNA, and a host of other cell nucleus antigens Circulating immune complexes

Defective regulatory mechanism

Overview of the pathogenesis of SLE

Skin cell

T cell T cell

B cell

APC

APC

Defective IC clearance

UV light Infection

External AgSelf Ag

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Typically, but not always, the onset is Typically, but not always, the onset is acuteacute.. SLE is an SLE is an uncommon disorderuncommon disorder,,

WomenWomen >> menmen (in a ratio of about 9 : 1) (in a ratio of about 9 : 1) . .The most common( initial complaints) are:

Fever , fatigue and weight loss + skin rash+ arthritis= ??? SLE

Skin manifestationsSkin manifestations::The The classic rash classic rash of acute SLE is an erythema of the cheeks and nose in the rough shape of acute SLE is an erythema of the cheeks and nose in the rough shape

of a butterfly, with facial swelling. Occasionally, a few blisters may be seenof a butterfly, with facial swelling. Occasionally, a few blisters may be seen..Some patients Some patients develop widespread discoid papulosquamous plaques very like those of develop widespread discoid papulosquamous plaques very like those of discoid LEdiscoid LE . .

About About 20% of patients20% of patients, have , have no skin no skin disease at any stagedisease at any stage . .Other dermatological features includeOther dermatological features include::

peri-ungual telangiectasia, erythema over the digitsperi-ungual telangiectasia, erythema over the digits,, hair fall hair fall (especially at the frontal margin of the scalp), and (especially at the frontal margin of the scalp), and photosensitivityphotosensitivity..

UlcersUlcers may occur on the palate, tongue or buccal mucosa may occur on the palate, tongue or buccal mucosa..

PresentationPresentation

Malar rash: This is a "butterfly-shaped" red rash over the cheeks may be worsen by sun exposure

Discoid lupus These are red, raised patches

with scaling of the overlying

skin.

Maculopapular eruption

Oral ulcer:

•Painless sores in the nose or mouth

Alopecia

periungualtelangiectasia ., erythema over the digits

Raynaud’s phenomenon is commonly found in lupus. It lack specificity.

(a triphasic reaction of distal digits to cold or emotion, in which the skin colour changes from white to blue to red)

InvestigationsInvestigationsConduct a full physical examination, looking for internal diseaseConduct a full physical examination, looking for internal disease . .

Biopsy of skin Biopsy of skin lesions is worthwhile because the lesions is worthwhile because the histopathologyhistopathology and iand immunopathologymmunopathology are distinctive are distinctive..

H/P H/P ;There is usually some ;There is usually some thinning of the epidermisthinning of the epidermis, liquefaction , liquefaction degeneration of epidermal basal cells, and a mild perivascular degeneration of epidermal basal cells, and a mild perivascular mononuclear cell infiltratemononuclear cell infiltrate..

DIFDIF ; ;is helpful: IgG, IgA ,IgM, and C3 are found individually or is helpful: IgG, IgA ,IgM, and C3 are found individually or together in a together in a band-like pattern band-like pattern at at BMZBMZ of of involved skin involved skin and often and often

uninvolved skin uninvolved skin as well ,as well , whereas with DLE only in involved skin.

--ANA is positive in up to 100%ANA is positive in up to 100%--Double stranded DNA positive in 50-70%Double stranded DNA positive in 50-70%

--Ro (SSA) and La(SSR) may be positive (e.g. 20%) if ANA Ro (SSA) and La(SSR) may be positive (e.g. 20%) if ANA negativenegative

--Cardiolipin is positive in subsets with recurrent abortions, Cardiolipin is positive in subsets with recurrent abortions, thrombosis and livido reticularisthrombosis and livido reticularisA) positive LE cells or B) raised anti-native DNA antibdy binding or C) anti-Sm antibody or D) false positive serological test for syphilis.

--Histone is positive in drug induced casesHistone is positive in drug induced cases

Antibody screeningAntibody screening::

The The skin changes skin changes may be may be transienttransient, , continuouscontinuous or or recurrentrecurrent; ; they correlate well with the they correlate well with the activityactivity of the systemic disease of the systemic disease . .

Internal involvement can be Internal involvement can be fatalfatal, but the overall prognosis now is, but the overall prognosis now is for about three-quarters (3/4) of patients to survive for 15 yearsfor about three-quarters (3/4) of patients to survive for 15 years..

Renal Renal involvement suggests a poorer prognosisinvolvement suggests a poorer prognosis..

CourseCourse

SLE is a great imitatorSLE is a great imitator . .--Its Its malarmalar rash can be confused with rash can be confused with sunburnsunburn, , polymorphic light polymorphic light

eruption and rosaceaeruption and rosacea . .--The The discoid lesions discoid lesions are distinctive, but are also seen in DLE and are distinctive, but are also seen in DLE and

in SCLEin SCLE . .Occasionally, they look like Occasionally, they look like psoriasispsoriasis or or lichen planuslichen planus . .

--The The hair fall hair fall suggests telogen effluviumsuggests telogen effluvium . .--Plaques on the scalp may cause a scarring alopeciaPlaques on the scalp may cause a scarring alopecia..

SLE should be suspected when a SLE should be suspected when a characteristic rash characteristic rash isis combined with combined with fever, malaise and internal diseasefever, malaise and internal disease..

Differential diagnosisDifferential diagnosis

Criteria for diagnosing lupus

The diagnosis of lupus is a clinical one made by observing symptoms .

Lab tests provide only a part of the picture. The American College of Rheumatology has designated 11

criteria for diagnosis .

To receive the diagnosis of lupus, a person must have 4 or

more of these criteria :

1. Serositis:

2 .Oral ulcers3 .Arthritis:

4. Photosensitivity:

5. Blood disorder.

6 .Renal disorder

7 .Immunologic disorder

8 .Antinuclear antibody Positive

9 .Neurological disorder.:

10 .Malar rash

11 .Discoid rash

( SOAP BRIAN MD)

Criteria of the ARA for the classification of SLE

person shall be said to have SLE if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval or observation.

TreatmentTreatment

Local TherapySun protection

topical steroidssteroids . .

topical calcineurin inhibitors

Intralesional SteroidSteroid

Systemic TherapyAntimalarialAntimalarial

Systemic steroidssteroids..

Immunosuppressive agents Immunosuppressive agents e.g; e.g; Azathioprine (Imuran) . Mycophenolate mofetil (MMF)

Biologic therapies : anti-TNF medications (etanercept, infliximab) in the treatment of recalcitrant CLE, particularly SCLE

Subacute cutaneous lupus erythematosus Subacute cutaneous lupus erythematosus SCLE

This is This is less severe less severe than acute SLE, but is also often associated with than acute SLE, but is also often associated with Some systemic diseaseSome systemic disease

Skin lesions of SCLE : are annular or psoriasiformThe clinical skin lesions are the distinctive featureof SCLE

Patients with SCLE may have some of the criteria of SLE as defined by the ARA, including:

photosensitivity, arthralgias ,serositis, renal disease, and serologic abnormalities.

50% of patients with SCLE have SLE.All cases have anti-Ro (SS-A) antibodies.Most have anti-La (SS-B) antibodies.Serious organ involvement of SLE is uncommon.

.

CourseCoursethe course is the course is prolonged prolonged as in SLEas in SLE . .

The skin lesions are slow to clear but, in contrast to DLE, do so The skin lesions are slow to clear but, in contrast to DLE, do so with little or with little or no scarringno scarring..

ComplicationsComplicationsSystemic disease is frequent, but not usually seriousSystemic disease is frequent, but not usually serious..

ChildrenChildren born to mothers who have, or have had, this condition born to mothers who have, or have had, this condition are liable to are liable to neonatal LE neonatal LE with transient annular skin lesions and with transient annular skin lesions and permanent heart blockpermanent heart block..

Differential diagnosisDifferential diagnosisThe morphology is characteristic, but lesions can be mistaken for The morphology is characteristic, but lesions can be mistaken for psoriasispsoriasis or widespread or widespread DLEDLE..

Annular lesions may resemble Annular lesions may resemble tinea corporis tinea corporis or figurate or figurate erythemaserythemas..

InvestigationsInvestigationsPatients with Patients with SCLESCLE should be evaluated in the same way as those should be evaluated in the same way as those with acute SLE, although deposits of immunoglobulins in the skin with acute SLE, although deposits of immunoglobulins in the skin and antinuclear antibodies in serum are present less often (80%)and antinuclear antibodies in serum are present less often (80%)..Many have antibodies to the cytoplasmic antigen Ro (SS-A)Many have antibodies to the cytoplasmic antigen Ro (SS-A)

TreatmentTreatmentSCLE SCLE does better with does better with antimalarialsantimalarials, such as hydroxychloroquine , such as hydroxychloroquine

, than acute SLE, than acute SLE . .Oral retinoids are also effective in some casesOral retinoids are also effective in some cases..

Systemic steroids may be needed tooSystemic steroids may be needed too..

DLE Discoid lupus erythematosusDiscoid lupus erythematosus::

The The most common most common form of LEform of LE lie mostly on lie mostly on sun-exposed skin sun-exposed skin of the of the faceface, , scalp scalp and and earsears . .

PresentationPresentationOne or two plaques only, or many in several areasOne or two plaques only, or many in several areas

PlaquesPlaques show erythema, scaling, follicular plugging (like a nutmeg gratershow erythema, scaling, follicular plugging (like a nutmeg grater))..They are well demarcatedThey are well demarcated . .

heal with ScarringScarring and atrophy, telangiectasia, hypopigmentation and atrophy, telangiectasia, hypopigmentation and a peripheral zone of hyperpigmentationand a peripheral zone of hyperpigmentation..

CourseCourse--The disease may spread relentlessly, but in about half of the The disease may spread relentlessly, but in about half of the

cases the disease goes into remission over the course of several cases the disease goes into remission over the course of several yearsyears . .

--ScarringScarring is common and hair may be lost permanently if there is is common and hair may be lost permanently if there is scarring in the scalpscarring in the scalp . .

--Whiteness remains after the inflammation has cleared, and Whiteness remains after the inflammation has cleared, and hypopigmentation is common in dark skinned peoplehypopigmentation is common in dark skinned people . .

--Discoid LE rarely progresses to SLEDiscoid LE rarely progresses to SLE..

--Most patients with DLE remain wellMost patients with DLE remain well . .However, screening for SLE and internal disease is still neededHowever, screening for SLE and internal disease is still needed..

--A A skin biopsy skin biopsy is most helpful if taken from an untreated plaque is most helpful if taken from an untreated plaque where appendages are still presentwhere appendages are still present

--DIF DIF shows deposits of IgG, IgA,IgM and C3 at the BMZshows deposits of IgG, IgA,IgM and C3 at the BMZ . .Biopsies for Biopsies for DIFDIF are best taken from older untreated plaques are best taken from older untreated plaques . .

--Blood tests Blood tests are usually are usually normalnormal

occasionally ANA +ve in 35%occasionally ANA +ve in 35%..

InvestigationsInvestigations

Differential diagnosisDifferential diagnosisPsoriasisPsoriasis is hard to differentiate from is hard to differentiate from DLEDLE when its plaques first when its plaques first arise but has larger thicker scales, and later it is usually arise but has larger thicker scales, and later it is usually

symmetrical and affects sites different from those of discoid LEsymmetrical and affects sites different from those of discoid LE . .

DLEDLE is more common on the face and ears, and in sun-exposed is more common on the face and ears, and in sun-exposed areas, whereas psoriasis favors the elbows, knees, scalp and areas, whereas psoriasis favors the elbows, knees, scalp and sacrumsacrum..

DLEDLE is far more prone than psoriasis to scar and cause hair loss is far more prone than psoriasis to scar and cause hair loss . .

Histopathology of DLE:

--Sun avoidance and screens Sun avoidance and screens are importantare important potent or very potent topical corticosteroidspotent or very potent topical corticosteroids . .

It is justifiable to use them on the face, as the risk of scarring is It is justifiable to use them on the face, as the risk of scarring is worse than that of atrophyworse than that of atrophy . .

--intralesional injections of triamcinolone intralesional injections of triamcinolone (2.5 or 10 mg/mL)(2.5 or 10 mg/mL) If discoid LE does not respondIf discoid LE does not respond..

Oral Oral antimalarials FOR antimalarials FOR Stubborn and widespread lesions Stubborn and widespread lesions ssuch uch as hydroxychloroquine, but rarely these cause irreversible eye as hydroxychloroquine, but rarely these cause irreversible eye

damagedamage . .The eyes should therefore be tested before and at intervals during The eyes should therefore be tested before and at intervals during

treatmenttreatment . .--

TreatmentTreatment

Dermatomyositis is a subset of Dermatomyositis is a subset of polymyositispolymyositis with distinctive with distinctive skinskin changeschangesHad a Characteristic; (Erythematous & Edematous changes in the Skin) + (Muscle Weakness & Inflammation )

There are There are adult adult and and juvenilejuvenile types typesWhen starting after the age of 40, dermatomyositis may signal an When starting after the age of 40, dermatomyositis may signal an

internal malignancyinternal malignancy . .

--The cause is unknown but an autoimmune mechanism seems The cause is unknown but an autoimmune mechanism seems likelylikely . .

Autoantibodies to striated muscle are foundAutoantibodies to striated muscle are found-.-.

DermatomyositisDermatomyositis

11 . .Skin signs ; Skin signs ; are characteristicare characteristic . .FaceFace;;

Typical patients have a Typical patients have a faint lilac discoloration faint lilac discoloration around their around their eyes (eyes (sometimes called sometimes called ‘heliotrope‘heliotrope’ because of the color of the flower)’ because of the color of the flower)..

Malar erythema Malar erythema and and edemaedema Sometimes , less striking erythema of the neck and presternal areaSometimes , less striking erythema of the neck and presternal area . .HandHand; ;

Gottron’s papules Gottron’s papules in most patients (in most patients (lilac slightly atrophic papules over the lilac slightly atrophic papules over the knuckles of their fingers)knuckles of their fingers)

Streaks of erythema Streaks of erythema over the over the extensor tendons of the handextensor tendons of the hand, , peri-ungual telangiectasiaperi-ungual telangiectasia

PresentationPresentation

22 . .Weakness of proximal muscles Weakness of proximal muscles in many patients, but not all. in many patients, but not all. Including ; climbing stairs, getting up from chairs and combing the Including ; climbing stairs, getting up from chairs and combing the hair become difficulthair become difficult..

The skin signs usually appear at the The skin signs usually appear at the same time same time as the muscle symptoms but, as the muscle symptoms but,

occasionally, appear months or even years occasionally, appear months or even years earlierearlier . .

Sometimes, the skin signs appear in isolationSometimes, the skin signs appear in isolation . .

Raynaud’s phenomenonRaynaud’s phenomenon, arthralgia, dysphagia and calcinosis , arthralgia, dysphagia and calcinosis may followmay follow . .

The rash may become The rash may become scalyscaly and, rarely, and, rarely, itchyitchy; eventually that on ; eventually that on the light-exposed areas and overlying involved muscles develops the light-exposed areas and overlying involved muscles develops poikilodermapoikiloderma..

InvestigationsInvestigationsMuscle enzymes Muscle enzymes levelslevels such as aldolase and creatinine such as aldolase and creatinine

phosphokinase (CPK) are often elevatedphosphokinase (CPK) are often elevated..

Muscle imaging : Muscle imaging : MRI is the method of choice for diagnostic imaging of muscle abnormalities in patients with myositis.ElectromyographyElectromyography (EMG) detects muscle abnormalities (EMG) detects muscle abnormalities Muscle biopsy Muscle biopsy shows inflammation and destruction shows inflammation and destruction..

The ESR is elevated in about ½ of patients Elevated anti-nuclear antibody (ANA) levels in 40% - 80%

Adult dermatomyositis or polymyositis requires a search for an Adult dermatomyositis or polymyositis requires a search for an underlying malignancyunderlying malignancy..

In In childrenchildren the disorder is often self-limitingthe disorder is often self-limiting..

in in adultsadults it may be prolonged and progressive it may be prolonged and progressive..

Features of mixed connective disease may developFeatures of mixed connective disease may develop . .

The presence of The presence of calcinosiscalcinosis suggests a good prognosis suggests a good prognosis..

CourseCourse

ComplicationsComplicationsMyositis may lead to Myositis may lead to permanent weakness permanent weakness and and immobilityimmobility, and , and

inflammation to inflammation to contracturescontractures or or cutaneous calcinosiscutaneous calcinosis . .

Some die from progessive and severe myopathySome die from progessive and severe myopathy..

Differential diagnosisDifferential diagnosisOther connective tissue disorders may look similar, particularly Other connective tissue disorders may look similar, particularly mixed connective tissue disease and SLEmixed connective tissue disease and SLE..

) ) In LE, the finger lesions favor the skin between the knuckles whereas in In LE, the finger lesions favor the skin between the knuckles whereas in

dermatomyositis the knuckles are preferreddermatomyositis the knuckles are preferred( .( .

TreatmentTreatment

Local TherapySun protection

topical steroidssteroids

Daily use of a medicated shampoo . .

Topical antipruritic agents

effective moisturization regimens

Systemic TherapyAntimalarialAntimalarial

Systemic steroidssteroids

Methotrexate, Cyclosporine and cyclophosphamide

Anti -TNF-α therapy and other Biologic therapies

Morphoea is a localized form of sclerodermaMorphoea is a localized form of sclerodermapale indurate plaques pale indurate plaques on the skin but on the skin but no no internal sclerosisinternal sclerosis . .

Many plaques are surrounded by a Many plaques are surrounded by a violaceous haloviolaceous halo . .

The The cause cause is unknown , except that Lyme borreliosis may be is unknown , except that Lyme borreliosis may be associated with the disease in Europe but not in the Americasassociated with the disease in Europe but not in the Americas . .

Types: 3 clinical type:Circumscribed,

Linear Frontoparietal: with or without hemiatrophy of

the face. (rare type)(rare type)..

PrognosisPrognosis is usually is usually goodgood, and the fibrosis slowly clears leaving , and the fibrosis slowly clears leaving slight depression and hyperpigmentationslight depression and hyperpigmentation..TreatmentsTreatments include include : :topical steroids, calcipotriene, psoralen with ultraviolet A (PUVA)topical steroids, calcipotriene, psoralen with ultraviolet A (PUVA) , ,

MorphoeaMorphoea

(en coup de sabre) Linear scleroderma occurring on the face

Systemic sclerosis: (Systemic scleroderma) :In this disorder the skin becomes hard as connective tissues thicken

Face & Hands (most frequently) but the change may extend proximally to involve the forearms & upper arms,

Face: facial appearance: is characteristic - :

- The forehead is smooth & shiny - The forehead lines are expressless. - The nose becomes small & pinched .

- The mouth opening is constricted & radial furrows appear. - Small, mat – like telangiectases are frequently found on

the face, occur in 75% of patients ..

Hands & forearms

Atrophy occurs 1st in the pulps of the fingers & small painful ulcers are formed, heal with scars ,the nails are curving over the atrophic phalanges .

Paronychia is commonPigmentation occurs in a bout 50% of the patients .forearm’s skin will be thinner than normal .

Leg ulcers occur in 40% of the patients

Loss of pulp substance,

periungual telangiectasias,

painful digital ulcer and sclerotic skin (flecks of calcium extruding)

PresentationPresentationMost patients suffer from Raynaud’s phenomenon and Most patients suffer from Raynaud’s phenomenon and

sclerodactylysclerodactyly . .

Their fingers become immobile, hard and shinyTheir fingers become immobile, hard and shiny . .

Some become hyperpigmented and itchy early in their diseaseSome become hyperpigmented and itchy early in their disease . .

Peri-ungual telangiectasia is commonPeri-ungual telangiectasia is common..

The diagnosis is made The diagnosis is made clinicallyclinically because histological because histological abnormalities are rarely present until the physical signs are well abnormalities are rarely present until the physical signs are well establishedestablished..Laboratory tests Laboratory tests should includeshould include : :fluorescent ANA testfluorescent ANA test

X-raysX-rays of the hands of the handsMuscle enzymes Muscle enzymes measurementmeasurement

Antibody Scl-70 TestAntibody Scl-70 Test immunoglobulin levelsimmunoglobulin levels,,

blood count blood count and ESRand ESRThe evaluation of the heart, kidney, lungs, joints andThe evaluation of the heart, kidney, lungs, joints andmuscles associated sclerodermamuscles associated scleroderma..

Barium studies Barium studies are are best avoided best avoided as obstruction may follow poor as obstruction may follow poor evacuationevacuation . .

InvestigationsInvestigations

CourseCourseAs the disease progresses, sclerosis spreads to the As the disease progresses, sclerosis spreads to the faceface, , scalpscalp

and trunkand trunk . .Most have abnormalities of the Most have abnormalities of the gut gut including dysphagia, including dysphagia, oesophagitis, constipation, diarrhoea and malabsorptionoesophagitis, constipation, diarrhoea and malabsorption..

Fibrosis of the Fibrosis of the lungslungs leads to dyspnoea leads to dyspnoea. .

Fibrosis of the Fibrosis of the heartheart to congestive failure to congestive failure.. The The kidneyskidneys are involved late, but this has a grave prognosis are involved late, but this has a grave prognosisfrom malignant hypertensionfrom malignant hypertension..

Differential diagnosisDifferential diagnosisThe differential diagnosis includes The differential diagnosis includes chilblainschilblains and and

erythromelalgiaerythromelalgia . .

The systemic sclerosis should be distinguished from that ofThe systemic sclerosis should be distinguished from that of widespread morphoeawidespread morphoea , ,

porphyria cutanea tardaporphyria cutanea tarda,, mixed CT diseasemixed CT disease , ,

eosinophilic fasciitiseosinophilic fasciitis , ,diabetic sclerodactyly anddiabetic sclerodactyly and an acute arthritis with swollen fingersan acute arthritis with swollen fingers . .

RarelyRarely the disease is mimicked by scleromyxoedema, the disease is mimicked by scleromyxoedema, amyloidosis or carcinoid syndromeamyloidosis or carcinoid syndrome..

..

TreatmentTreatmentThis is unsatisfactoryThis is unsatisfactory . .

The calcium channel blocker The calcium channel blocker nifedipinenifedipine may help Raynaud’s may help Raynaud’s phenomenonphenomenon..

Systemic steroids, salicylates, antimalarials and longterm penicillin Systemic steroids, salicylates, antimalarials and longterm penicillin are used, but are not of proven valueare used, but are not of proven value . .

d-penicillamine has many side-effects, especially on renal d-penicillamine has many side-effects, especially on renal functionfunction . .Physiotherapy is helpfulPhysiotherapy is helpful ; ;

photopheresis is experimentalphotopheresis is experimental.. Recently, there have been promising reports of the efficacy of Recently, there have been promising reports of the efficacy of

ultraviolet A-1ultraviolet A-1))340340––400400 nmnm ( (phototherapy for affected skin in systemic sclerosisphototherapy for affected skin in systemic sclerosis..

Most complications are caused by the Most complications are caused by the involvement of organs involvement of organs other than the other than the skin,skin, but ulcers of the fingertips and calcinosis are but ulcers of the fingertips and calcinosis are distressingdistressing..

Hard skin immobilizes the joints and leads to contracturesHard skin immobilizes the joints and leads to contractures

ComplicationsComplications

This is a variant of systemic sclerosisThis is a variant of systemic sclerosisRelatively good prognosisRelatively good prognosisFluorescent ANA test (indirect IF) : : nuclear centromeresnuclear centromeres The mnemonic stands for The mnemonic stands for CCalcinosisalcinosis, R, Raynaud’aynaud’s phenomenon, s phenomenon, EEsophageal sophageal dysmotility, dysmotility, SSclerodactylyclerodactyly and and TTelangiectasiaelangiectasia..

Telangiectasia is peri-ungual on the fingersTelangiectasia is peri-ungual on the fingersand flat, mat-like or rectangular on the faceand flat, mat-like or rectangular on the face . .

Many patients with this syndrome develop a diffuse progressive Many patients with this syndrome develop a diffuse progressive systemic sclerosis after months or yearssystemic sclerosis after months or years..

CREST syndromeCREST syndrome

Mixed connective tissue diseaseMixed connective tissue diseaseThis is an overlap between This is an overlap between SLE SLE and either and either sclerodermascleroderma or or polymyositispolymyositis..PresentationPresentationAs in LE, women > menAs in LE, women > men..Many develop swollen hands and sclerodactyly, and skin lesions like those of Many develop swollen hands and sclerodactyly, and skin lesions like those of cutaneous LE may also be presentcutaneous LE may also be present . .AlopeciaAlopecia is mild and the hair fall mimics telogen effluvium is mild and the hair fall mimics telogen effluvium . .Peri-ungual telangiectasia and pigmentary disturbances are commonPeri-ungual telangiectasia and pigmentary disturbances are common . .

About 25% of patients have a About 25% of patients have a small vessel vasculitis small vessel vasculitis with with palpable purpurapalpable purpura, , leg ulcers leg ulcers and and painful dermal nodules painful dermal nodules on the hands or elbowson the hands or elbows . .Many show Raynaud’s phenomenon, arthritis, serositis and myositisMany show Raynaud’s phenomenon, arthritis, serositis and myositis . .

Headaches, weakness, fatigue, lymph node enlargement or hoarseness occur Headaches, weakness, fatigue, lymph node enlargement or hoarseness occur in about one in three patients; renal and central nervous system disease are in about one in three patients; renal and central nervous system disease are

less commonless common..

CourseCourseThe disorder is chronic, and usually turns into either SLE or The disorder is chronic, and usually turns into either SLE or systemic sclerosissystemic sclerosis..

Differential diagnosisDifferential diagnosisThe disorder can be confused with SLE, dermatomyositis, The disorder can be confused with SLE, dermatomyositis, polymyositis, systemic sclerosis and other sclerosing processes polymyositis, systemic sclerosis and other sclerosing processes such as porphyria cutanea tardasuch as porphyria cutanea tarda

InvestigationsInvestigations

Antinuclear antibody is usually raised.Anti-double-stranded DNA is usually, but not always, negative.Anti-RNP Ab is almost always raised. DIF: of involved and uninvolved skin shows IgG within the epidermal nuclei, also in a speckled DIF: of involved and uninvolved skin shows IgG within the epidermal nuclei, also in a speckled patternpattern..

Only one-third of patients have subepidermal immunoglobulin deposits in involved skinOnly one-third of patients have subepidermal immunoglobulin deposits in involved skinCXR is used to assess for infiltrates, effusion or cardiomegaly.ECG is used to exclude myocardial infarction.Echocardiogram may be required to rule out effusion. .

Most have hypergammaglobulinaemiaMost have hypergammaglobulinaemia , , oesophageal dysmotilityoesophageal dysmotility , ,

abnormal pulmonary function tests andabnormal pulmonary function tests andPositive rheumatoid factorPositive rheumatoid factor . .HypocomplementaemiaHypocomplementaemia,,CBC:CBC: leucopenia, anaemia,leucopenia, anaemia, high ESR high ESR cryoglobulinaemia andcryoglobulinaemia and

falsepositivefalsepositive biological tests for syphilis occur in a few patients biological tests for syphilis occur in a few patients..

TreatmentTreatmentTreatment depends upon which organs are involved, but systemic Treatment depends upon which organs are involved, but systemic steroids are usually needed, in the same dosage as for SLE. steroids are usually needed, in the same dosage as for SLE. Immunosuppressive agents reduce the dosage of systemic Immunosuppressive agents reduce the dosage of systemic steroids, and NSAIDs help with arthralgia, myalgia and swelling of steroids, and NSAIDs help with arthralgia, myalgia and swelling of the handsthe hands..

Other connective tissue diseasesOther connective tissue diseasesRheumatoid arthritisRheumatoid arthritis

Most patients with rheumatoid arthritis have no skin disease, but Most patients with rheumatoid arthritis have no skin disease, but some have tiny fingertip infarcts, some have tiny fingertip infarcts, purpura, ulcers, palmar or peri-purpura, ulcers, palmar or peri-

ungual erythema, orungual erythema, or pyoderma gangrenosumpyoderma gangrenosum . .The most common skin manifestations are marble-like nodules The most common skin manifestations are marble-like nodules near jointsnear joints..

These are always associated with the presence of rheumatoid These are always associated with the presence of rheumatoid factor. Some patients with rheumatoid arthritis have a vasculitis of factor. Some patients with rheumatoid arthritis have a vasculitis of larger blood vessels with deep ‘punched out’ ulcers on the legslarger blood vessels with deep ‘punched out’ ulcers on the legs..

Relapsing polychondritisRelapsing polychondritisThis process can affect any cartilage as the disorder is apparently This process can affect any cartilage as the disorder is apparently caused by autoimmunity to collagencaused by autoimmunity to collagen..

The ears are the usual target. The overlying skin becomes red, The ears are the usual target. The overlying skin becomes red, swollen and tenderswollen and tender . .

The cartilage in joints, the nose and the tracheo-bronchial tree The cartilage in joints, the nose and the tracheo-bronchial tree may be involved, so that patients develop floppy ears, amay be involved, so that patients develop floppy ears, asaddle nose, hoarseness, stridor and respiratory insufficiencysaddle nose, hoarseness, stridor and respiratory insufficiency..Aortic aneurysms are also seenAortic aneurysms are also seen . .Treatment is with systemic steroids and NSAIDsTreatment is with systemic steroids and NSAIDs . .

Tracheostomy may be necessaryTracheostomy may be necessary..