tissues diseases are auto-immune diseases, in which the connective
tissue, is the primary site of involvement. These diseases are
characterized by marked cutaneous and systemic manifestations.
types of connective tissue diseases
group there is damage of connective tissue as a result of complex
immunological reactions involving autogenous antigens.
includes systemic lupus erythematosus, rheumatic fever, systemic
sclerosis and dermatomyositis.
group of connective tissue diseases
such as in Ehlers-Danlos syndrome.
group as in scurvy
or senile elastosis.
erythematosus is an auto-immune connective tissue disease. This group
includes systemic lupus erythematosus, which is characterized by
skin and multisystemic manifestations and discoid lupus erythematous
which has only cutaneous manifestations. It has been proposed that
genetic factors and somatic mutations be implicated in the
pathogenesis of the disease, in which immunoglobulins are present at
the dermo-epidermal junction.
lupus erythematosus is an auto-immune disease, which is benign but
has a very chronic course. The disease affects females more than
males, any age group may have the disease but adults are more
affected than children.
The onset of
the lesions may be precipitated by a variety of factors such as
mental stress, trauma, infection, excessive exposure to sunlight,
PUVA therapy, drugs such as isoniazid and griseofulvin.
reddish, scaly, hyperkeratotic, well-defined patches of
various-sized, appear on sun exposed areas mainly on face, hands and
scalp. The lesions are characterized with follicular plugging known
as “stibbling,” adherent scales and horny plugging, which have
occupied dilated pilosebaceous canals. Follicular plugging is
has a chronic course and tend to heal with atrophy, scarring and
the scalp lead to permanent cicatricial alopecia. Telengectasia is a
common manifestation and the lesions usually show hyperpigmentation
at the borders.
Fig. 294. Discoid lupus erythematosus
Fig. 295. Discoid lupus erythematosus
Fig. 296. Cicatricial alopecia
Fig. 297. Lupus erythematosus
(Butter fly lesion)
e: Discoid Lupus
Erythematosus :Skin scarring& cicatricial alopecia
lupus erythematosus has a characteristic clinical, laboratory and
changes include five cardinal signs
Hyperkeratosis with keratotic plugs.
of the stratum malpighii.
Liquification degeneration of the basal cells.
Basophilic degeneration of the collagen.
perivascular lymphocytic infiltrate.
Leucopenia, thrombocytopenia and biological false positive
reaction (BFB) for syphilis may be positive.
cell tests is usually negative in DLE
DLE has to
be differentiated from different skin diseases:
DLE may become extensive covering wide areas of the skin simulating
systemic lupus but without systemic involvement of internal organs
and usually shows negative LE test.
light eruption: The
lesions are more superficial, scarring is minimal if it happens,
have a shorter course than DLE, and the eruption is polymorphous.
sites involved are the seborrheic areas. The skin lesion is sharply
demarcated, greasy, scaly patches and heal without scarring or
Dry silvery scaly patches showing neither atrophy nor scarring.
measures are very important.
the patient from direct exposure to sunlight and using sunscreens
especially on the seashores.
Extreme heat and cold
exacerbate the preexisting lesions.
oral steroids or chloroquine helps some.
LUPUS ERYTHEMATOSUS (SLE)
This is an
immune connective tissue disease that has a familial tendency,
marked immune dysfunction and characterized by multisystmes
involvement. The disease may affect any age group especially adult
females. Immunoglobulins, predominantly IgG, but less frequently IgM
and IgA, together with complement (C1, C3) can be demonstrated at
the dermo-epidermal junction by immunofluorescence techniques.
usually accompanied by vague and fleeting general symptoms such as
intermittent low-grade fever, abdominal and thoracic pain, weakness,
fatigue, and arthralgia. These symptoms may continue for a long time
before skin lesions appear or will not be accompanied by any skin
usually begins on the more exposed parts of the skin presenting with
erythematous, purpuric macules and telengectasia.
appear in about half of the cases in the form of superficial, dusky
lesions on the sun exposed areas mainly on the face that give the
butter fly appearance. The lesions may be unilateral but usually
bilateral and symmetrical. Usually there is no atrophy of lesions as
Purpura is a
common manifestation of SLE.
Fig. 298. Systemic lupus erythematosus
Fig. 299. Systemic lupus erythematosus
usually of the remitting type.
abdominal and chest pain,
which is related to internal organs involvement.
anemia, and thrombocytopenia due to bone marrow depression.
polyarteritis is due to involvement of serous and synovial
membranes. Polyarthritis and purpura are important signs of SLE.
Fig. 300. Systemic lupus erythematosus
(Dusky, erythematosus and
hematuria, mild albuminuria, hypertension and edema due to
thickening of the glomelular capillaries with focal necrosis known
as wire loop lesions.
signs of pericarditis, myocarditis, and endocarditis leading to
vegetative lesions of the valves known as “Limban Sacks
changes: may be
generalized involving most blood vessels of skin and internal organs
leading to different and complex manifestations.
Epilepsy and convulsions.
SYSTEMIC LUPUS ERYTHEMATOSUS
is a rare syndrome occurring in infants of mothers with
Features of Neonatal SLE
have large annular erythematous lesions or discoid lesions that may
be present at birth but always develop within the first 2 months,
sometimes being precipitated by sunlight.
the lesions may be purpuric on both the face and trunk.
improves after 4-6 months and completely clears within a year
neonatal LE may occasionally develop SLE in the second decade.
Neonatal LE can occur in successive pregnancies. It has long been
known that the LE-cell factor and antinuclear antibodies could cross
the placenta and may be demonstrated in the newborn for as long as 3
months without harming the child.
babies with congenital heart disease have a one in three chance of
developing SLE or other connective-tissue disease.
factors can be detected in most cases and can be used for prenatal
manifestations as heart block, hepatospleenomegaly, anemia,
thrombocytopenia and arthritis, may be associated with the skin
central nervous system involvement is rare in children but may
LUPUS ERYTHEMATOSUS IN CHILDHOOD
picture, course and treatment are similar to the disorder in adults.
The earliest age of onset reported is 3 months.
may resemble chronic bullous disease of childhood.
organs are involved mainly the kidneys showing diffuse proliferatve
nephritis, central nervous system manifestations,
hepatospleenomegaly and lymph nodes enlargement are common in
children, affected by SLE.
Findings in SLE
Albuminuria, hematuria and casts.
ESR is elevated.
thrombocytopenia and hemolytic anemia.
false positive (BFP) for syphilis may be positive.
ration is usually reversed with increased gamma globulins.
complement fixation test may be positive
Anti-nuclear antibody (ANA) test is positive
fluorescent band test: a band of fluorescent immunoglobulin can be
detected at the dermo-epidermal junction, which gives bright
yellow green fluorescence.
Intradermal test: purified nuclear antigen shows strong reaction
to histone and nucleoproteins
Test: LE cell is a peculiar cell which is a neutrophilic polymorph
nuclear leucocyte engulfing in its cytoplasm homogenized purple
staining inclusion body. LE Cell may appear as rosette shape. LE
Cell test is positive in SLE and some cases of other connective
SYSTEMIC LUPUS ERYTHEMATOSUS
cases and during severe exacerbation:
exposure to sun:
should be avoided and the patients are advised to wear broad-brimmed
hats, to cover the ‘V‘ shape area of the neck and the arms and
to use a sunscreen preparation.
overexertion and secondary infection should be avoided.
may be required for symptomatic treatment taking care to avoid drugs
that may exacerbate the condition, especially antibiotics, which are
usually needed to combat infections. Estimation of C-reactive
protein may be helpful: a level higher than 60 mg suggests
may give some relief for urticarial lesions, bullous eruptions and
drugs: Hypertension must be treated and it is generally agreed
that hydrallazine can be used safely in most patients with SLE.
Nephrotic syndrome or cardiac failures need diuretics. . Low C3
often indicates severe renal disease.
It should be noted that not all patients require steroids. Some
fulminating cases have been treated with massive doses of steroids
but the advantages of such therapy rarely outweigh the risks.
60 mg per day, is the steroid of choice initially. Once the
condition appears to be under control, the dose may be reduced
gradually, until maintenance dose of about 5-15 mg per day is
It has been
claimed that a single dose daily or on alternate days, before a meal
or with milk before bedtime, produces fewer side effects and does
not impair the therapeutic response.
and azathioprine, or prednisone and Cyclophosphamide can give also
good results in renal involvement.
erythrocyte sedimentation rate (ESR) is no guide to the adequacy of
therapy. The titers of antinuclear antibodies often persist
unchanged despite clinical remission.
antibody and serum complement levels may be helpful in predicting
myopathy can occur with high doses.
high dosage of corticosteroids, for example, 60 mg of prednisone
daily for 6 months, is said to improve the renal lesions more than
small suppressive doses. This improvement of survival is not seen in
patients with raised blood urea before the onset of therapy.
There is no
evidence that steroids are prophylactic and that prolonged therapy
will prevent the development of new features.
enzymes are usually normal but urinary creatine is increased
is a good sedative,
for cases accompanied by psychosis.
may be very useful, particularly in patients with joint
manifestations. There is an increased risk of aspirin hepatotoxicity
may improve arthritis. Corticosteroids are required in the acute
cases and should be given in adequate dosage.
drugs: In mild cases
the administration of chloroquine or hydroxychloroquine may allow
the dose of steroids to be reduced.
are less useful than in DLE and for long-term therapy may be
dangerous causing photosensitivity.
not contra-indicated, as healthy live babies have been delivered
from women on antimalarial therapy throughout pregnancy.
cases not responding to prednisolone
responding to systemic steroids can be treated by the following
drugs have been used for adult patients not responding to
corticosteroids but their use should be given to selected cases.
Immuno-suppressive drugs are not given to the young age groups having
It has been
concluded that azathioprine added nothing to high-dose prednisone
treatment in mild or moderate renal disease. Sudden withdrawal may
be followed by relapse.
may be a more
effective immuno-suppressant but it is more toxic than azathioprine.
Tripple therapy with prednisone plus azathioprine and
Cyclophosphamide had no therapeutic advantage over prednisone and
has been found helpful. Some reports claim excellent results of
prednisone combined with Chlorambucil.
this drug is given in a dose of 7.5 mg weekly which has improved
steroid-resistant patients. The long-term risk of malignancy must be
considered, whenever immunosuppressive drugs are used.
cases not controlled by prednisolone and immuno-suppressive drugs.
of systemic lupus erythematous that are not controlled by prednisone
and immuno-suppressive drugs, can be put under the following type of
therapy with 1g methylprednisone is given intravenously in 500 ml
normal saline over 4 h on three successive days to inpatients may be
may be required for patients with the lupus or anticardiolipin
antibodies who have thrombotic episodes.
400-600 mg daily may help some patients.
SYSTEMIC LUPUS ERYTHEMATOSUS
skin eruptions of systemic lupus erythematosus are uncommon. The
clinical manifestations are similar to that of bullous pemphigoid
and dermatitis herpetiformis.
the bullae are subepidermal with a neutrophilic infiltrate
occasionally resulting in micro-abscesses resembling dermatitis
(IF) shows linear bands of IgG, IgA and IgM and C3 in the basement
CAUSED BY TRANSPLACENTAL TRANSFER OF
manifestations in the neonates have now been reported in a number of
maternal disorders that are believed to be induced by circulating
autoantibodies. Of particular interest to the dermatologist are
those reports concerning lupus erythematosus, pemphigus vulgaris,
herpes gestationis and aphthosis.
IgM and IgE antibodies do not cross the placenta in significant
amounts; this phenomenon is restricted to diseases caused by
autoantibodies of IgG class.
does not pass across the placenta. Complement can be detected in the
fetus from about the 11th week of gestation.
is catabolized more or less completely within the first 3-6 months
of life, and antibody-mediated transplacental diseases can be
expected to remit spontaneously within this period.
is an autoimmune connective tissue disease involving skin and
muscles. Children and older age groups may be affected with the
disease that may be fatal in some cases.
skin and muscle manifestations appear in dermatomyositis, which may
have vague signs and symptoms making diagnosis more difficult.
two types of dermatomyositis, the juvenile and the adult type.
childhood, where it has the same manifestation as the adult type
with some differences.
phenomenon is rare in childhood.
more extensive than the adult type.
childhood is better than in adults.
characteristic skin manifestations are:
cyanotic erythema, erythematous scaly macules or urticarial lesions
appear on any site of the skin surface mainly on the face with
swollen eyelids. Other skin manifestations mimic those of
disseminated lupus erythematosus leading to atrophy and
telengectasia; subcutaneous calcification or scleroderma like of the
chronic cases the skin lesions are in the form of:
lichenoid scaly papules with telengectatic cyanotic atrophy
resembling lichen planus, mainly on the back of hands, knees and
extensor surfaces of the limbs. These lesions may show pigmentation
membrane of the mouth shows aphthous like lesions.
of the scalp leads to cicatricial alopecia.
involved are mainly those of the proximal extremities that become
swollen, tender and painful where the inflammatory changes end in
systemic manifestations appear according to the muscles involved as
dyspnea, dysphagia, diplopia, myocarditis, hepatosplenomegaly and
exudates like patches of cotton wool like and hemorrhage appear on
anemia, leucocytosis and increased sedimentation rate. Serological
tests for syphilis are negative in contrast to systemic lupus, which
show positive tests.
L.E test is
enzymes such as aldolase, creatine and phosphokinase are elevated.
lupus erythematosus, scleroderma, erysipelas and myasthenia gravis.
picture: skin, muscle and other organ involvement.
biopsy: usually is diagnostic showing degenerative changes in the
muscle with fragmentation, hyalinization with vacuoles and
connective tissue is thick, condensed and increased in thickness.
shows: edema, homogenization, fibrosis, and sclerosis.
fibers are destroyed.
structure is atrophic.
dermatomyositis is usually unsatisfactory. There is high
mortality rate. The current available treatments are corticosteroids
and immuno-suppressive drugs.
is an autoimmune connective tissue disease characterized by
cutaneous thickening due to changes in the dermal connective tissue.
The disease is either localized to the skin or systemic, involving
the skin and other organs.
characterized by single or multiple, ovoid, slightly raised, firm
and thickened off-white patches mainly on the trunk and extremities
Skin lesions have a cyanotic edge with hyper or hypopigmentation.
a very chronic course and spontaneous resolution may take years
leaving residual atrophy and pigmentation.
mainly in children and young age. The skin manifestations are ovoid
thickened patches with slightly raised cyanotic edge.
in children is usually accompanied by muscle and bone atrophy and
occasionally with spina bifida.
Fig. 301. Morphea
discrete, sclerotic small lesions occur on the chest and trunk.
This is an
autoimmune sclerotic disease, affecting mainly middle the aged females.
Multisystem involvements and increase in the antinuclear factor
characterize the disease.
vary greatly according to the specific organs involved. There is
ischaemic atrophy in different skin sites and other systems.
lesions are in the form of large plaques on the chest and limbs
having the clinical features of morphea.
may leave fibrotic, pigmented and atrophic areas, while other types
may manifest with blistering.
contracture of the skin and limitation of mobility mainly around the
mouth, leading to peri-oral wrinkles, small mouth and difficulty in
contracture of the eyelids is accompanied by limiatation of the skin
mobility, are common manifestations.
appears mainly on the face and hands.
pigmentation as that of Addison‘s disease, may accompany some
ischaemia leads to micro-infarcts of the finger pulps; loss of
finger prints pattern with thromboses and dilated nail folds
capillaries, where later there is tapering of the fingers and nail
atrophy with ulceration and gangrene.
pain, swelling, inflammation of muscles, ankylosis and
to muscle involvement leading to limitations of movement and
contracture deformities interfering with mastication. The skin of
the face becomes thin and parchment-like, resulting in a peak-like
nose and mask face appearance.
resorption of bones and calcium deposits in the muscles is a common
fibrosis and bundle branch block.
phenomenon is common.
common and different degrees of lung impairment.
dysphagia and reflux are common, due to limitation of the esophagus
mobility, dilatation of the stomach, pyloric stenosis and mal-
manifestations and systemic involvement are usually diagnostic.
phenomena and sclerodactaly.
erythrocyte sedimentation rate.
LE Cell is
antinuclear factor besides the other manifestations are important
data that can help to reach the diagnosis.
false positive reaction for syphilis may be positive.
fluorescence technique: thready pattern in the nuclear material may
of the skin.
to affection of respiratory muscles.
Death usually occurs from
cardiac or acute renal failure.
treatment: Analgesics and anti-rheumatics (Isobrufen) may give
relief to joint and muscle pain.
extracts, antihistamines, calcium disodium versenate, and potassium
para-amino-benzoic acid are some of the different medications were
used for treatment. Different reports concerning the actual value of
these medications were reported but some are not convincing.
and immunosuppressive drugs are of limited values.
250 mg daily for three months may give some improvement.
sclerosus is a sclerosing immune connective tissue disease,
affecting all ages and is associated with auto-antibodies (organ
lesion is polygonal, white slightly raised papule with central
depression representing the follicular plugging. Purpura is also a
manifestation due to loss of vascular support as a result of
degeneration of the dermal collagen.
sites involved are the back and front of the trunk. Anogenital areas
may be involved leading to sclerosis and atrophy of the anal and
histologic changes are characteristic. These include liquefaction
degeneration of the basal layer, epidermal atrophy, hyperkeratosis
and follicular plugging as that of lupus erythematosus.
fibromatoses include a group of well-defined clinical entities that
affect the skin.
fibromatoses affects infants and children.
is characterized by
proliferate activity of the fibroblasts.
Fig. 302. Fibromatoses
There is a
tendency to local recurrence but, unlike fibrosarcomas, they do not
types of fibromas affecting infants and children are:
hamartoma of infancy.
Calcifying aponeurotic fibromas.
myofibroma is a rare connective tissue disease-affecting infant and
may be present at birth and continue to appear for several months.
are due to increased fibrous tissue growth forming nodules in the
subcutaneous tissues and bones mainly on the head, neck and trunk.
nodules may affect liver, heart and lungs. The nodules may be
rubbery or hard, and may be superficial or deep, invading the
nodules have good prognosis, but if the viscera are involved, the
infant usually dies within few months.
of chemotherapy with Vincristin, Actinomycin D and Cyclophosphamide
may give good results.
HEMARTOMA OF INFANCY
as a solitary lesion that affects boys much more often than girls.
It is present at birth or develops during the first 3 years. The
commonest site involved is the axillary and shoulder region,
followed by the groin.
presents as a subcutaneous mass, which may enlarge steadily up to a
size of 15 cm.
after excision is infrequent and, if left untreated spontaneous
regression may occur.
This is a
disorder of glycosaminoglycan synthesis.
are present at birth or develop in early childhood. There may be
small pearly papules or nodules, particularly on the face or neck.
Large subcutaneous tumors may also occur, particularly on the scalp.
These may be hard or soft, fixed or mobile, and they may ulcerate.
hypertrophy is commonly present, and flexion contractures of the
fingers, elbows, hips and knees may develop.
lesions can occur in the skull, long bones or phalanges lead to
musculature is poorly developed.
changes show deposition of amorphous hyaline material.
condition persists into adult life that leads to joint contractures