The specific and diagnostic skin lesions are
represented by acute, subacute, and chronic cutaneous L.E.
The most frequent chronic cutaneous L.E. skin disorders
are represented by the discoid form (DLE). Data gathered over the last
ten years in the Institute of Clinical Dermatology at the University of
Florence, Italy, has shown up a mean incidence of around 15 new cases per
annum. This survey of 157 DLE cases demonstrated that females are more
often struck, with a female to male ratio of 3:1, and the average age at
onset is about 44 years. As well-known, DLE presents with a triad of morphological
manifestations: the first clinically appreciable lesion is an erythema
that usually has the characteristic of being a slackening erythema of violet
coloration that often presents a modest penetrational element. Following
the erythema, a hyperkeratosis appears, white-greyish, extremely adherent
to the skin that also involves dilated pilosebaceous follicles, whose removal,
difficult and painful because of a hyperalgesia of the skin, allows the
detection of tiny, pointed, horny formations on their ventral surfaces.
Much later, the third of the elements characterizing this form of the disease
appears, that is to say the atrophy that usually begins in the center of
the lesions. More rarely, other morphological changes are also possible
such as pigmentation alterations (hyperchromatism, sometimes associated
with hypochromic areas) and telangiectasis. Two kinds of DLE are distinguishable:
the circumscribed or localized form (the more common type, representing
65% of cases in our casebook) and the generalized form (35%).
The localized form is recognized by the appearance of
one or few blotches, preferentially distributed on the face, external ear
and scalp (alopecia cicatrisata).
The generalized form is characterized by the advent of
several lesions which, as well as the face, are located on the trunk (III
superior) and more rarely on the limbs. Such a distinction is of great
clinical interest because, almost exclusively, the generalized forms are
associated with sero-immunological changes and may present with a systemic
engagement.
The face is the most favored location (74% of DLE cases)
after which, the next most common target is the scalp (20%). In 8.2% of
these latter cases, the DLE is located exclusively on the scalp, determining
the lupoid alopecia cicatrisata picture. In order of frequency, following
the scalp location, the next site is the auricle of the external ear (17.2%);
in 1.9% of these cases the involvement of the ala auris is the only manifestation
in the course of the DLE. Another rare site is in correspondence with the
palmar and plantar surfaces (1.2%); scleroatrophy often prevails in these
locations, while hyperkeratosis is modest. A new acute phase for the skin
disorders is frequent in DLE patients following photo-exposure, which is
documented in around 75% of cases.
Patients, especially those with the generalized form of
DLE, can sometimes present with some skin irregularities that surround
the ungual lamina, such as erythema and telangiectasia which may now and
then be associated with punctiform micro-hemorrhages. These modest and
often asymptomatic peri-ungual lesions should be carefully checked out
since their detection very frequently represents a prognostic and evolutive
indication of particular gravity.
In the survey of 157 DLE cases undertaken
by the Florence Clinic, this clinical “marker” was regularly associated
with forms of generalized DLE that presented with the clinical characteristics
of systemic engagement. Concerning this, it is important to point out that
in 6-10% of the patients having systemic lupus erythematosus (SLE), the
“entrance” manifestation is a DLE, and also that 25-33% of the SLE patients,
during the course of their illness, present a skin picture that has the
hallmarks of DLE.
The histopathological profile of
chronic discoid L.E. is very evocative and is therefore a useful
aid in the diagnosis. Histopathological diagnosis is based on the identification
of the following alterations: follicular hyperkeratosis of the ortokeratose
kind with dilated pilosebaceous follicles, liquefacient degeneration of
the basal keratinocytes, superficial and periadnexal perivascular lymphomonocytic
infiltration. In the epidermis there is often a modest edema in the initial
phase whereas a slight atrophy is documentable in the late stages. Much
rarer varieties of chronic cutaneous L.E. are the hypertrophic discoid
L.E. conditions, also called “warty”, which present with lesions that are
prominent and rugged to the touch due to the prevalence of hyperkeratotic
phenomena. The favored site for these lesions is the extensor surface on
the limbs. In the tumid form, there is no hyperkeratosis whereas dermal
cell infiltration seems to prevail. An extremely rare form is the erosive
variety, also characterized by scleroatrophic lesions and which is especially
to be found on the palmar and plantar surfaces.
Lupoid panniculitis or profound
lupus erythematosus is marked out by
the presence of circumscribed, subcutaneous, nodular formations having
a tough-elastic consistency, with a tendency to become chronic and resolved
with depressed scars. The nodules may be located on the face, scalp, chest,
buttocks, upper and lower extremities. These lesions are often associated
with other L.E. skin disorders, particularly DLE-type lesions. Histological
changes are represented by a lymphocytic infiltration which penetrates
into the septa and subcutaneous adipose tissue. The adipose lobules run
into hyalinization and a peculiar alteration of the infiltrating lymphocytes
is often seen, known as “lymphocytic nuclear dust”. Lupoid panniculitis
is a septal lymphocytic panniculitis unaccompanied by vasculitic phenomena.
Subacute cutaneous L.E. (SCLE) is
almost a females-only condition, with a major incidence among the
20-40 year-olds. It accounts for about 10% of the entire cutaneous L.E.
survey conducted at Florence’s dermatology clinic.
Morphologically, it is characterized by the appearance,
in the initial phases, of a small erythematous element, orbicular and of
a few centimeters diameter, slightly infiltrated and covered by thin furfuraceous
scaling; the progressive extension of this initial lesion and the arrival
of others determines the clinical expression of the two most common morphological
types: papulosquamous and annular-polycyclic. The former is distinguished
by the presence of numerous papulosquamous, erythematous, orbicular elements
that tend to be grouped together and to give rise to characteristic reticulated
figurations. This variety is also known as psoriasiform because of the
particular distinctness of the squamous component.
In the annular-polycyclic type,
the initial papuloid-erythematous element
heads towards extension in a centrifugal direction and resolution in the
central part, thus determining the formation of rings or festoons which,
because of the confluence, can lend a typical polycyclic aspect. SCLE is
prevalently located on the extensor surface of the hands, forearms and
upper arms, deltoid regions and in correspondence with the anterior and
posterior thorax regions (upper third), the face usually being spared.
A worsening of the skin lesions is often found when there is emotional
stress or exposure to ultra-violet radiation: photosensitivity is in fact
another distinctive mark of subacute L.E.
Sometimes, the SCLE is associated with other specific
skin disorders such as those found in the chronic discoid form and in the
acute type. Much more frequently, however, are non-specific manifestations
like non-cicatricial alopecia, reticular livedo, Raynaud’s phenomenon,
the presence of periungual telangiectases. It has recently been demonstrated
that, in individuals who are genetically so disposed, some drugs can bring
about the onset of SCLE. The drugs responsible for this are principally
the thiazides, followed by piroxicam, penicillamine, glyburide, aldactone,
griseofulvin, procainamide, oxyprenol. A proportion varying between 46
and 78% of SCLE cases present with enough clinico-serological characteristics
to be able to be classified as an SLE, according to the ARA criteria. However,
these SCLE/SLE patients only rarely have a serious prognosis. In fact,
renal and central nervous system involvement is only found in 20% of such
cases. Sontheimer, studying a great number of SCLE patients’ case histories,
identified the following risk factors for the development of a serious
form of SCLE: the papulosquamous variety, co-existence of the acute and
subacute forms, resistance to anti-malarial therapy, the presence of circulating
anti-dsDNA antibodies, and persistent hypocomplementemia.
Histopathologically, SCLE presents a similar pattern
to the discoid form, the differences only being quantitative.
Changes in the epidermis are usually modest and are represented
by vacuolization of the basal layer keratinocytes and, in the more advanced
stages, by a modest atrophy. In the psoriasiform variety, it is possible
to demonstrate an orthokeratotic hyperkeratosis that is completely absent
in the annular-polycyclic form.
Sebaceous follicle dilatation is usually absent. as are
the intrafollicular corneous roots.
Perivascular and periadnexal infiltration of lymphocytes
and monocytes is much more modest and superficial than that occurring in
DLE. It is held that only in 75-80% of cases is it possible, in an exclusively
histological way, to differentiate a form of DLE from a type of SCLE.
Acute cutaneous L.E., in its diverse
clinical expressions, is found only in the active phases of an SLE
and is substantially represented by: butterfly malarerythema, maculopapularerythema,
a bullous variety.
The butterfly rash is the most common form, involving
the zigomatic area though sparing the nasogenial sulci, and is characterized
by an erythema of rapid onset, not uncommonly photodependent and coinciding,
in its arrival, with the exacerbation of the systemic disease.
The erythema takes on variable tones from red-bluish
to a rosy lilac, there can be light infiltration and a modest furfuraceous
peeling, it lasts a short time (hours or a few days) and disappears leaving
a complete and pristine restoration.
Much rarer is the skin picture composed of the appearance
of multiple erythematous patches, associated with an infiltrating and purpuric
component and extended to the face, extensor surface of the limbs and the
upper third of the trunk.
Likewise uncommon is the bullous variety of acute L.E.
that especially affects young males and which is characterized by the presence
of a vesicobullous rash which developes without the formation of milia
and scleroatrophic lesions and which usually involves the upper part of
the trunk and particularly the neck and supraclavicular regions.
These blisters can be like those in herpetiform dermatitis
in the form of small elements grouped together on an edematous-erythematous
background or, more rarely as in bullous pemphigoid, as cavitary lesions,
taut and with serosanguinous contents. An important clinical characteristic
with these lesions is their fast and resolvent therapeutic response to
diaminodiphenylsulphone (DDS). On the basis of immunopathological reports,
two varieties of bullous SLE have recently been distinguished: type I is
characterized by the presence of circulating antibodies directed against
an antigen of 145-290 KD (collagen VII). These antibodies, fixed on by
a substrate represented by normal human skin subjected to chemical cleavage
with NaCl 1M, demonstrate an exclusive deposition on the dermal side. The
antibodies fixed in vivo can be detected in I.F.D. under the form of a
linear deposit of IgG at the dermal-epidermal junction, and in immunoelectronmicroscopy
as a deposit in the dense sublamina region. Type II presents the usual
clinical and histological patterns as the preceding form but there are
no demonstrable circulating and fixed antibodies with the characteristic
anti-collagen VII autoantibodies.
The most commonly observed non-specific
and non-diagnostic manifestations of lupus erythematosus are: vascular
lesions, alopecia, pigmentation changes, sclerodactylia, and cutaneous
calcinosis.
These alterations may be found in the course of connective
tissue diseases and their identification does not therefore permit one
to diagnose L.E. However, these lesions are usually detected in the L.E.
forms having systemic involvement and often in the active phases of the
disease.
The most frequently noticed non-specific
skin disorders of L.E. are those that affect the vessels, whether
the tiny dermal vessels or the larger caliber ones located in correspondence
with the subcutaneous adipose tissue.
The involvement of the postcapillary
venules of the surface dermis is expressed with two kinds of skin
disorder: vasculitis urticaria and palpable purpura. The former is the
more common clinical variety, characterized by the appearance of long lasting
(48-72 hours) wheals having a purpuric component that heals with a desquamatory
outcome. There are typical histopathological (leukocytoclastic vasculitis)
and immunopathological (perivascular deposits of Ig and C) profiles that
correspond to this clinical aspect.
The palpable purpura is characterized by the presence
of purpuric elements, of small dimensions, multiple, with an infiltrating
component evident on palpation, localized on the lower limbs.
The involvement of the superficial dermal arterioles
determines small dermal infarcts, occurring frequently in the fingertips
(eponychium), while the involvement of larger diameter subcutaneous vessels
may cause subcutaneous nodules, chronic ulcers with a relapsing evolution,
reticular livedo and peripheral gangrene. And finally, the engagement of
the large subcutaneous venous vessels determines thrombophlebitis (the
finding of anti-phospholipid and anti-cardiolipin antibodies is common
in these cases).
Alopecia is another common non-specific lesion that can
accompany lupus erythematosus; lupoid cicatricial alopecia, as we have
already seen, is a typical clinicomorphological manifestation in DLE, located
on the scalp or, in males, the beard area. Non-cicatricial lupoid alopecia
may present itself in a widespread form or as a circumscribed type that
only involves the hair of the frontal region which appears to be thinned
out, shorter, finer and not comb-able.
This condition accompanies the active phases of the disease
while it tends to be resolved along with its clinical remission.
Paolo Fabbri
Direttore Clinica Dermosifilopatica II
Università degli Studi - Firenze |
Only Italian
English / Italian