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.