Al Azhar University Gaza Dr. lama khaled El Banna Faculty of Oral and Dental Medicine

1. Dermatology Lecture Notes, Eleventh Edition. Robin Graham-Brown, Karen Harman and Graham Johnston.
© 2017 John Wiley & Sons, Ltd. Published 2017 by John Wiley & Sons, Ltd.
I think my work is my attempt, I suppose, to try and
become a piece of connective tissue
Emma Thompson, actress
Lupus erythematosus
Lupus erythematosus is an autoimmune disorder that
occursintwomainforms:discoidlupuserythematosus
(DLE), in which the skin alone is affected, and ­systemic
lupus erythematosus (SLE), which affects both the skin
and the internal organs. A small proportion of patients
with DLE may subsequently develop SLE. A third vari­
ant, subacute cutaneous lupus erythematosus (SCLE),
is characterized by distinctive skin lesions that may be
associated with systemic features.
The pathogenesis of lupus erythematosus has not
been fully elucidated, but probably involves a combi­
nation of genetic factors predisposing to autoimmun­
ity and environmental agents, such as viral and
bacterial antigens, acting as triggering factors.
Discoid lupus erythematosus
Classically, DLE affects light‐exposed areas –
­principally the face and neck, but also the dorsa of
the hands and the arms. Lesions may be precipitated
or exacerbated by sunlight. Individual lesions con­
sist of scaling, erythematous plaques, with pro­
minent follicular plugging. If the scale is lifted off,
follicular plugs may be seen on its undersurface –
the so‐called ‘carpet‐tack’ (or ‘tin‐tack’) sign. There
may be only a few lesions, but extensive, cosmeti­
cally disfiguring involvement of the facial skin can
occur. Lesions heal with scarring, and the ­typical
picture is of an active, erythematous scaly margin
enclosing a central area of scarred, hypopigmented,
atrophic skin (Figure 18.1). The scalp may be
involved, producing areas of scarring alopecia in
which follicles are permanently destroyed.
Occasionally, the buccal or nasal mucosae are
affected.
Investigations
The diagnosis can be confirmed by skin biopsy.
Histology shows a lymphocytic infiltrate around
blood vessels, follicles and sweat glands, damage to
the basal layer of the epidermis, follicular plugging
and hyperkeratosis. Direct immunofluorescence of
lesional skin reveals granular deposits of immuno­
globulin G (IgG) and/or IgM at the dermoepidermal
junction. Some patients also have positive antinu­
clear and Ro & La antibodies, the ­significance of
which is unclear.
Connective tissue
diseases
18

2. Chapter 18: Connective tissue diseases 157
Treatment
Potent fluorinated topical steroids are helpful in many
cases, but if they are ineffective, intralesional injection
of triamcinolone or oral therapy with the antimalarial
hydroxychloroquine may be required. In severe exten­
sive disease, oral steroids, azathioprine and retinoids
may be of benefit. Light‐exposed areas should be pro­
tected by a sunscreen with a high sun protection factor
(SPF). Where there is extensive involvement of facial
skin, the use of cosmetic camouflage can be of benefit.
Systemic lupus erythematosus
This is a multisystem disorder that may affect the skin,
joints,heartandpericardium,lungs,kidneys,brainand
haematopoietic system. Typically, the disease affects
women, particularly of childbearing age, and pro­
gresses in a series of exacerbations and remissions.
Mucocutaneous lesions include oropharyngeal ulcer­
ation, diffuse alopecia, Raynaud’s phenomenon, vascu­
litis and photosensitivity. Often there is facial erythema
ina‘butterfly’distribution(Figure 18.2).The‘butterfly’is
representedby­erythemaonthecheekslinkedbyaband
of erythema across the nose. However, by far the most
common cause of this pattern of facial erythema is rosa­
cea (see Chapter 7).
Systemic manifestations include those listed in
the box.
Figure 18.1 Discoid lupus erythematosus (DLE):
irregular scaling, erythematous plaques and follicular
plugging have caused significant white scars.
Manifestations of systemic lupus
erythematosus
Polyserositis
• Arthralgia and arthritis (usually non‐erosive).
• Pericarditis.
• Pleurisy with effusions.
Nephritis
Central nervous system (CNS) involvement
• Psychosis and convulsions.
Haematopoietic abnormalities
• Haemolytic anaemia.
• Leukopenia.
• Thrombocytopenia.
Pyrexia, weight loss and general malaise
Figure 18.2 Facial erythema in systemic lupus
erythematosus (SLE).

3. 158 Chapter 18: Connective tissue diseases
Investigations
These should include a full blood count and bio­
chemistry, complement levels, urinalysis, electrocar­
diograph (ECG) and chest radiograph.
A number of autoantibodies may be found in
individuals with SLE. Antinuclear antibodies
(ANAs) at high titre are found in most, and anti‐
double‐stranded DNA antibodies (anti‐dsDNAs)
are characteristic. Others include anti‐Ro (also
known as anti‐SSA) and anti‐La (anti‐SSB) – which
are associated with neonatal lupus – and antiphos­
pholipid antibodies. A positive rheumatoid factor
and biological false‐positive serological tests for
syphilis may also be found.
Direct immunofluorescence of involved skin shows
the same pattern of immunoglobulin deposition seen
in DLE (see earlier).
Treatment
Systemic steroids and immunosuppressive agents
are the mainstay of treatment. Light‐exposed areas
of skin should be protected by sunscreens with a
high SPF.
Subacute cutaneous lupus
erythematosus
In this ‘subset’ of lupus, papulosquamous or annular
lesions occur on the upper torso and on light‐exposed
areas such as the backs of the hands and forearms.
The lesions do not scar, but leave considerable stain­
ing in their wake. Associated systemic features may
occur, but are usually mild. Antibodies to the Ro/SSA
antigen are a characteristic finding.
Antiphospholipid syndrome
This syndrome may be primary (Hughes’ ­syndrome)
or may occur with SLE. The main features are the
occurrence of recurrent miscarriage, venous throm­
boses, cerebral infarcts, thrombocytopenia and livedo
reticularis and cutaneous necrosis. These clinical
abnormalities are associated with the presence of
anticardiolipin antibodies and lupus anticoagulant
(subsets of antiphospholipid antibodies).
Neonatal lupus erythematosus
Neonatal lupus is associated with transplacental pas­
sage of maternal anti‐Ro and anti‐La antibodies. Its
features include skin lesions, thrombocytopenia,
hepatosplenomegaly and complete heart block.
Heart block persists, but the other features resolve as
maternal antibodies disappear from the infant’s
blood.
Drug‐induced systemic lupus
erythematosus
Drug‐induced SLE is uncommon. There are many
reports of a possible causal relationship, but the
drugs most firmly implicated include hydralazine,
procainamide, anticonvulsants (phenytoin, primi­
done), isoniazid, sulphasalazine, proton pump inhib­
itors and chlorpromazine.
Dermatomyositis
Heliotrope
A flower resembling the pale violet,
Which, with the Sun, though rooted‐fast, doth move
And, being changed, yet changeth not her love
Ovid
Dermatomyositis is an autoimmune inflammatory
disease of skin and muscle that may occur in child­
hood or in adult life. There are differences in the man­
ifestations of the disease in these two age groups.
Vasculitis and the late development of calcinosis are
features of the childhood disease that are not seen in
adults. In some adults, dermatomyositis is associated
with systemic malignancy, whereas there is no asso­
ciation with malignancy in the childhood disease.
Skin
The skin changes are as shown in the box.
Skin changes
• Violaceous erythema of the face and ‘V’ area of
the neck (Figure 18.3). This is said to ­resemble
the colour of the heliotrope flower and is
referred to as ‘heliotrope erythema’.
• Periorbital oedema and erythema.
• Erythema on the dorsa of the hands
and linear erythema on the dorsa of
the fingers (Figure 18.4). Erythematous
papules (Gottron’s ­papules) over the knuckles.
• Prominent, ragged cuticles and dilated
capillaries in the proximal nail folds (Figure 18.5).
• Erythema over the knees and elbows.
• In childhood, cutaneous vasculitis leading to
ulceration of the skin, particularly in the axillae
and groins.

4. 160 Chapter 18: Connective tissue diseases
series of patients, but the incidence seems to be
higher in older individuals. The preferred approach
to investigation appears to be performance of limited
screening, in the form of careful history, thorough
physical examination (rectal, lymph node, breast and
pelvic examinations), full blood count, stool occult
blood, cervical smear, chest radiograph and com­
puted tomography (CT) or MRI, as indicated by symp­
toms. In female patients, specific ovarian imaging is
advisable.
Treatment
In dermatomyositis associated with malignancy,
there is usually marked improvement when the neo­
plasm is excised. A relapse of the dermatomyositis
signals a recurrence.
The mainstay of therapy is oral corticosteroids,
often in combination with immunosuppressives
such as azathioprine, methotrexate or cyclophos­
phamide. Hydroxychloroquine is also used. If the
response is poor, intravenous immunoglobulin may
be tried. Recently, ­biologic agents have been used
with success. Where there is severe muscle involve­
ment, physiotherapy is an important adjunct to drug
therapy, in order to minimize contractures.
Scleroderma
Scleroderma means ‘thickening of the skin’, and refers
to a group of diseases in which there is sclerosis of the
skin and destruction of hair follicles and sweat glands.
Scleroderma may be an isolated cutaneous phenom­
enon, when it is called ‘morphoea’, or a cutaneous
component of a multisystem disorder.
Morphoea
Morphea is a disorder of unknown aetiology in which
there is sclerosis of the skin. It may be subdivided
clinically into the following types:
1 Circumscribed.
2 Linear.
3 Frontoparietal (en coup de sabre).
4 Generalized.
Circumscribed
This is the most common clinical presentation of
morphoea. Solitary or multiple indurated plaques
develop, predominantly on the trunk. Initially,
affected areas of skin have a violaceous hue, but they
gradually become thickened and ivory in colour
(Figure 18.6). The surface is smooth and shiny.
Eventually, usually after many months, the sclerosis
resolves, leaving atrophic, hyperpigmented areas.
Classification of scleroderma
• Morphoea: sclerosis of the skin without
systemic involvement.
• Systemic sclerosis: cutaneous sclerosis in
association with a vasculopathy of small
arteries, producing multi‐organ systemic
disease.
• Chemically induced scleroderma: sclerosis of
the skin as a manifestation of the toxic effects of
certain chemicals.
• Pseudoscleroderma: sclerosis of the skin
associated with a number of diseases other
than morphoea or systemic sclerosis.
Figure 18.6 Plaque of morphoea: a
solitary, well‐defined, thickened, shiny
ivory plaque on the trunk.

5. Chapter 18: Connective tissue diseases 161
Linear
Linear morphoea usually affects one limb, often
extending its full length. In childhood, it can signifi­
cantly impair the growth of the limb and produce
severe flexion deformities of large joints and digits.
Frontoparietal (en coup de sabre)
Resembling a sabre cut across the scalp and forehead,
this type of morphoea is a considerable cosmetic
problem. A linear, depressed, sclerotic area extends
from the face into the scalp, and is associated with loss
of hair along its length.
Generalized
There is extensive sclerosis of the skin on the trunk
and limbs. Flexion contractures restrict limb move­
ment, and if the chest is severely affected, breathing
may be impaired.
Treatment
Treatment is often of limited efficacy, but suggested
therapies include potent topical steroids, intrale­
sional steroid, topical vitamin D analogues, topical
calcineurin inhibitors, ultraviolet A (UVA) and meth­
otrexate. In linear morphoea on the limbs, physio­
therapy is essential to maintain joint motility, and
orthopaedic surgery may be necessary. Plastic sur­
gery can be of considerable cosmetic benefit in fron­
toparietal morphoea.
The natural history of morphoea is gradual sponta­
neous resolution.
Systemic sclerosis and CREST
syndrome
This is an autoimmune connective tissue disease of
unknown aetiology. It is a disorder in which sclerotic
changes in the skin occur as one component of a
multisystem disorder associated with a vasculopathy
of small arteries. In the most common form (some­
times referred to as the CREST syndrome: calcinosis,
Raynaud’s phenomenon, (o)esophageal involvement,
sclerodactyly and telangiectasia), skin changes affect
predominantly the face and hands.
Systemic involvement
Gastrointestinal
Dysphagia is the result of oesophageal involvement.
Damage to the myenteric plexus leads to hypomotility
of smooth muscle and later to atrophy and fibrosis,
resulting in impaired peristalsis. The gastro‐oesopha­
geal sphincter mechanism is also impaired, leading to
gastro‐oesophageal reflux, oesophagitis and eventual
stricture formation. Symptoms of oesophageal reflux
are common.
Atrophy and fibrosis of the smooth muscle of the
small bowel lead to impaired peristalsis, and the
resultant relative stagnation of small bowel contents
predisposes to bacterial overgrowth as colonic bac­
teria move upstream into the small intestine. Gut
bacteria deconjugate bile salts (which are essential
for micelle formation), and this leads to fat malab­
sorption and steatorrhoea. Occasionally, patients
present with a picture simulating acute intestinal
obstruction.
Similar pathology affects the large bowel and leads
to the formation of multiple wide‐mouthed
pseudodiverticula.
Pulmonary
An inflammatory alveolitis is followed by pulmo­
nary fibrosis, and disease of small pulmonary arter­
ies leads to pulmonary hypertension and cor
pulmonale.
Cutaneous features of systemic sclerosis
(Figure 18.7)
Face
• The facial skin is sclerotic and bound to
underlying structures, producing a tight,
shiny appearance, with loss of facial wrinkles,
a beaked nose and restriction of mouth
opening.
• Perioral furrowing (‘purse‐string mouth’).
• Facial telangiectasia.
• Loss of lip vermilion.
Hands
• Raynaud’s phenomenon.
• Tight sclerotic skin, producing progressive
contractures of the digits (sclerodactyly).
• Finger pulp infarcts, producing small, painful
ulcers. These infarctive changes lead to
progressive pulp atrophy and resorption of
the underlying terminal phalanges.
• Calcinosis.

6. 162 Chapter 18: Connective tissue diseases
Renal
Fibrinoid changes in arteries and arterioles are asso­
ciated with proteinuria and hypertension. Renal
involvement is usually mild, but in some cases it is
severe and rapidly progressive, and leads to renal
failure.
Nervous system
Neurological involvement is uncommon, but carpal
tunnel syndrome and trigeminal neuropathy have
been reported.
Cardiac
Myocardial fibrosis, conduction disorders and a vari­
ety of ECG abnormalities have been described.
Hepatic
There is a significant association between systemic
sclerosis and primary biliary cirrhosis.
Musculoskeletal
Arthralgia and arthritis occur in some patients, and
myopathy and inflammatory myositis may also occur.
Treatment
No therapy is known to alter the overall course of sys­
temic sclerosis, but many components of the disease
may be helped significantly by specific measures.
Digital ischaemia may be helped by electrically
heated gloves and socks. Calcium channel blockers
may help relieve Raynaud’s phenomenon, and ilo­
prost infusions are used for more severe ischaemia.
Patients with oesophageal reflux should avoid lying
flat, and treatment with proton pump inhibitors may
be very effective. Broad‐spectrum antibiotics are help­
ful in treating patients with gut bacterial overgrowth
and malabsorption. The use of angiotensin‐converting
enzyme (ACE) inhibitors is of significant benefit in
renal disease. In interstitial pulmonary disease, cyclo­
phosphamide is effective, and bosentan is of benefit for
pulmonary arterial hypertension.
Prognosis
Severe pulmonary or renal involvement is a poor
prognostic factor, although treatment is improving,
but most patients with systemic sclerosis live for
many years.
(a)
(b)
(c) (d)
Figure 18.7 Cutaneous features of systemic sclerosis: (a) facial appearance, (b) perioral telangiectases and
(c) finger pulp uclers and scars. (d) Radiograph showing calcinosis in a digit.