CUTANEOUS LUPUS
Lupus erythematosus is a
multisystem, idiopathic connective tissue disease that can have variable and
unique clinical cutaneous findings. Cutaneous lupus may be considered as a
spectrum of skin disease. Many variants have been described. Discoid lupus,
subacute cutaneous lupus, tumid lupus, lupus panniculitis, neonatal lupus,
lupus chilblains, and systemic lupus erythematosus (SLE) all have morphologically
distinctive cutaneous findings. Lupus is a heterogeneous disease with a wide
continuum of clinical involvement, from purely cutaneous disease to
life-threatening SLE. The cutaneous findings are often the first presenting
signs, and recognition of the skin manifestations can help make the diagnosis
of lupus.
SLE is the most severe form of lupus. Its clinical
course and outcome vary, from mild forms to severe, life-threatening variants.
In the most severe cases, the pulmonary, cardiac, neurological, and connective
tissue and integumentary systems are affected. Death may occur from renal
failure. Severe arthritis and skin findings are often present. SLE is diagnosed
by fulfillment of criteria that have been established by the American College
of Rheumatology. Variations in meeting these criteria from one patient with SLE
to the next are responsible for the varying clinical spectrum of disease.
Patients with lupus can have many laboratory abnormalities. These include
anemia of chronic disease and an elevated erythrocyte sedimentation rate.
Antinuclear antibodies (ANA) are found in some subsets of lupus, with almost
100% of patients with the systemic form testing positive for ANA. Many other,
more specific antibodies are found in patients with SLE, including anti-Smith
antibodies and anti–double-stranded DNA antibodies. Patients with renal disease
often have hypertension, elevated protein levels in their urine, and an
elevated creatinine level.
Clinical Findings: Many variants of cutaneous lupus exist, each with its own
morphological findings. Lupus is more common in women; it can be seen at any
age but is most frequently observed in early adulthood. However, lupus is
common enough that it is not infrequently seen in males. Neonatal lupus is a
rare form that occurs in neonates born to mothers with lupus.
Discoid lupus is one of the easiest forms of cutaneous
lupus to recognize. It is most commonly found on the head and neck region and
has a tendency to be present within the conchal bowl of the ear. Lesions are
often found in patients with SLE. Discoid lupus may occur as an entirely
separate disease with no other systemic or clinical findings of lupus. Fewer
than 10% of these patients eventually progress to the systemic form of lupus.
Discoid lesions are exacerbated by sun exposure, more specifically by exposure
to ultraviolet A (UVA) light. The lesions tend to have an annular configuration
with varying amounts of scale. The lesions can produce alopecia, and there is
almost always some amount of atrophy present. Follicular plugging is commonly
seen in discoid lupus. It is noticed clinically as a dilation of the follicular
orifices. Follicle plugs can also be seen by gently removing the scale from a
discoid lesion. On close inspection of the inferior side of the scale, one will
notice minute keratotic follicular plugs. This finding is specific for discoid
lupus and has been termed the “carpet tack sign,” because it resembles tiny
outreaching tacks. This sign can be easily missed if the scale is removed too
quickly or not inspected closely enough. Discoid lesions in darker-skinned
individuals may also have varying amounts of hyperpigmentation. Most patients
have some erythema and hyperpigmentation. Most patients present with a few
discoid lesions and are said to have localized discoid lupus. Those rare
patients with widespread disease have generalized discoid lupus. This variant
is rare, and such patients are much more likely than those with localized
disease to go on to fulfill the criteria for SLE at some point. The alopecia
seen in discoid lupus is scarring in nature, and the hair that has been lost
will not regrow even with aggressive therapy. Alopecia can be life-altering and
can cause significant psychological morbidity.
Subacute cutaneous lupus erythematosus is seen in a
subset of patients and has a higher incidence of developing into full-blown SLE
compared with other forms of cutaneous lupus. There are variants of subacute
cutaneous lupus, with the annular form and the papulosquamous form being the
two most common and most important to recognize. The annular form manifests
with pink to red annular patches that slowly expand and coalesce into larger,
interconnected polycyclic patches. They occur most commonly on sun-exposed skin
of the face and upper trunk. The papulosquamous version also manifests in
sun-exposed regions. It appears as smaller, pink-red patches with overlying
scale. Both forms are exacerbated by sun exposure and are pruritic. They heal
with no scarring.
Neonatal lupus is an uncommon form of lupus that can
manifest with or without cutaneous findings. However, cutaneous findings are
the most universal clinical finding in neonatal lupus, occurring in more than
90% of those affected. The most common scenario is a child born to a mother who
has not yet been diagnosed with lupus. Neonatal lupus can manifest with varying
degrees of congenital heart block, and this is the most serious sequela. Some
children require a pacemaker to control the arrhythmia. Thrombocytopenia is
also one of the more frequent effects of neonatal lupus. Neonatal lupus is
directly caused by the transplacental migration of anti-Ro (anti-SSA)
antibodies and, to a lesser extent, anti-La (anti-SSB) antibodies. The
antibodies are only transiently present, because the newborn does not produce any
new antibodies. Therefore, neonatal lupus improves over time, and most children
have no long-term difficulties. The cutaneous findings in neonatal lupus
include pink to red patches or plaques, predominantly in a periorbital
location. The rash resolves with time, and if any residual skin finding
remains, it is that of fine telangiectases in the location of the patches and
some fine atrophy. The telangiectases and atrophy tend to improve as the child
enters adulthood.
Lupus panniculitis (lupus profundus) is a rare cutaneous
manifestation of lupus. It manifests as a tender dermal nodule, more commonly
in women. A large percentage of patients with lupus panniculitis have been
reported to go on to develop SLE. The overlying skin may appear slightly
erythematous to hyperpigmented, but there is no appreciable surface change. The
dermal nodules tend to slowly enlarge with time. The diagnosis can be made only
by biopsy, because the clinical picture is not specific. Biopsies of these
dermal nodules are best performed with an excisional technique to obtain
sufficient tissue for diagnosis. The inflammation is entirely confined to the
subcutaneous tissue. The histological differential diagnosis of lupus
panniculitis is often between lupus and cutaneous T-cell panniculitis. The
diagnosis requires the use of both clinical and histological information. The
histological evaluation often requires immunohistochemical staining to help
differentiate the lesions from those of other mimickers. Lesions of lupus
panniculitis often heal with atrophic scarring.
Tumid lupus is a rare clinical variant of cutaneous
lupus that typically manifests as a red dermal plaque on a sun-exposed surface
of the skin. Clinically, it can appear similar to polymorphous light eruption, lymphoma,
pseudolymphoma, or Jessner’s lymphocytic infiltrate. The plaques are
exacerbated by ultraviolet light exposure. They are frequently asymptomatic to
slightly tender but rarely pruritic. They tend to wax and wane, with the worst
outbreaks occurring in the spring- time and remissions in the winter.
Histologically, the infiltrate as been found to be more of a CD4+
T-cell infiltrate.
Lupus chilblains is a unique form of Raynaud’s
phenomenon, and it is identical in clinical presentation to pernio. It may be
that this is just pernio occurring in a patient with lupus. Lupus chilblains
and pernio manifest typically on the distal extremities, the toes being the
most commonly affected region. The patient develops tender, cold, purplish
papules and plaques. The rash is exacerbated by cold and wet environments.
Treatment includes keeping the regions dry and warm by
avoiding cold exposure. Patients diagnosed with pernio probably should undergo
screening for lupus, because a small percentage of them actually have lupus
chilblains. Histological evaluation of lupus chilblains shows a dense
lymphocytic infiltrate with some areas of thrombosis of small vessels and a
lymphocytic vasculitis.
The cutaneous findings seen in SLE are vast and can
overlap with other forms of cutaneous lupus. Although the systemic findings are
responsible for the morbidity and mortality, the cutaneous findings are often
the presenting sign, and, if the clinician is aware, they can help make the
diagnosis. The most important of the cutaneous skin findings in SLE is the
malar rash. This rash manifests as a tender, pink-to-red plaque or patch on the
cheeks and nose, mimicking the shape of a butterfly; hence, it has been termed
the “butterfly rash of lupus.” It is commonly mistaken for rosacea, and vice
versa. Rosacea typically affects a wider area of skin and is associated with
more telangiectases and papulopustular lesions. The malar rash of lupus also
spares the nasolabial fold, which is an important clinical finding and a
discriminating objective discovery. It is typically more prominent during
systemic flares of the underlying SLE, and patients can appear very ill.
Patients are exquisitely photosensitive, and the rash is exacerbated by
exposure to ultraviolet light.
Discoid lupus is also seen as a manifestation of
systemic lupus, and it has the same clinical appearance as described earlier.
Raynaud’s phenomenon is well described, and a high percentage of patients with
SLE report those symptoms. Alopecia was long used to help make the diagnosis of
lupus. It is no longer part of the diagnostic criteria, but it can have
significant psychological impact on the patient. Nail and capillary nail fold
changes are seen if looked for. The true incidence of these findings is
unknown. Nail fold telangiectases and erythema are the two most common nail
findings. Nail pitting, ridging, and alterations in the color of the lunula
have also been reported. Lupus patients with nail changes have been found to
have a higher incidence of mucosal ulcerations, which are another of the mucocutaneous
findings of SLE. Livedo reticularis is a fishnet- like pattern found typically
on the lower extremities; it is a nonspecific finding but has been reported
commonly in lupus. It also occurs in many other skin and systemic diseases.
Histology: The
histological findings in all forms of lupus are similar, with specific forms
having some unique findings. Most forms show an interface dermatitis with
hydropic changes in the basilar layer of the epidermis. A superficial and deep
periadnexal lymphocytic infiltrate is almost universally seen. Other connective
tissue diseases (e.g., dermatomyositis) can have similar histological findings.
Discoid lupus may show scarring, atrophy, and follicular plugging along with
these other findings. Lupus panniculitis is unique in that the inflammation is
localized to the subcutaneous tissue. The diagnosis of lupus panniculitis is
difficult and requires a host of special stains and clinical pathological
correlation.
Treatment: The
treatment of cutaneous lupus is difficult and must be tailored to the patient
and the specific form of lupus. Potent topical corticosteroids may work for a
tiny lesion of discoid lupus, but they are not effective in lupus panniculitis.
Universal treatment of cutaneous lupus requires sun protection and sunscreen
use. The sunscreen used should block in the UVA range, because this is the most
active form of ultraviolet light that exacerbates lupus. Smoking should be
ceased
immediately, and patients should be screened routinely
by their family physician or rheumatologist for progression of the disease.
Specific therapies for cutaneous lupus include oral
prednisone and hydroxychloroquine or chloroquine as the typical first-line
agents. If these are unsuccessful, quinacrine can be added. Other agents that
have been reported to be effective include dapsone, isotretinoin, and
methotrexate.
