43 The Skin and Rheumatic Diseases

Many systemic rheumatologic conditions present with skin findings.

The differential diagnosis for skin findings may require a skin biopsy for clinical-pathologic correlation.

Systemic steroids should be avoided if possible in psoriasis because flaring may occur with tapering of systemic glucocorticoids.

New biologic therapies have substantially improved care of patients with severe and resistant psoriasis.

The neutrophilic dermatoses comprise a group of inflammatory diseases including pyoderma gangrenosum and Sweet’s syndrome, which can be associated with autoimmune diseases.

Patients with lupus erythematosus can have a wide variety of lupus-specific and lupus-nonspecific skin lesions.

Lupus-nonspecific skin lesions are more frequently seen in patients with systemic lupus erythematosus.

Patients with dermatomyositis frequently have pathognomonic skin lesions that may be seen in the absence of muscle disease.

Antimalarials may be of benefit for patients with morphea.

Diagnosis of Skin Lesions Associated with Rheumatic Diseases

The skin is a highly visible organ that is frequently affected in rheumatic diseases, and the presence of skin lesions may be helpful diagnostically. Certain caveats are worth noting before discussing the specifics. First, a major pitfall for the nondermatologist in evaluating skin lesions is incomplete knowledge of the entities in the differential diagnosis. For example, malar erythema occurs frequently in patients with systemic lupus erythematosus (SLE), but the differential diagnosis for malar erythema is rather extensive and includes conditions that are much more prevalent than lupus (e.g., rosacea), as well as conditions that are far less prevalent (e.g., Rothmund-Thomson syndrome). Patients frequently have more than one skin condition, which often makes diagnosis more challenging.

Another caveat for the nondermatologist concerns skin biopsy. Being able to determine when a skin biopsy is likely to be diagnostically useful in many cases requires a great deal of specialized knowledge, as does the interpretation of pathology reports. It is often the case with inflammatory skin conditions that the microscopic findings are actually less diagnostically specific than is the clinical examination. Unfortunately, it is common for a pathology report to list a diagnosis without providing context regarding how definitive were the findings. For example, a skin biopsy report may have psoriasis listed as the final diagnosis, but, depending on the specific case, the unstated additional possibilities may include nummular dermatitis, atopic dermatitis, seborrheic dermatitis, lichen simplex chronicus, dermatophytosis, or drug eruption. Particularly with regard to inflammatory skin conditions, having a working knowledge of both dermatopathology and dermatology and placing the histologic findings in the context of the clinical presentation may be necessary to arrive at the correct diagnosis.

The above considerations notwithstanding, it is clearly useful for the physician caring for patients with rheumatic diseases to be well versed in their cutaneous manifestations. In this chapter, we provide an overview of these manifestations, as well as perspective on diagnosis and differential diagnosis. Therapy is discussed briefly in conditions where treatment may be specifically directed toward the skin lesions. Etiology and pathogenesis of these diseases are covered elsewhere in this text.

Psoriasis

Psoriasis is one of the most common inflammatory skin diseases, affecting about 2% of the general population. There is a wide range of severity of skin lesions, from a few relatively asymptomatic plaques to extensive, disabling disease. The onset may be at any time during life. Once present, it may exhibit exacerbations and remissions, but it does not tend to resolve permanently. In general, onset in childhood portends more severe disease.

Skin lesions of psoriasis characteristically are sharply demarcated plaques with silvery scale and underlying erythema, although there may be a paucity of scale if the lesions have been partially treated or if they occur in intertriginous areas. When the scale is removed, pinpoint bleeding may be observed (Auspitz sign). Lesions may occur in areas of trauma (Koebner phenomenon) such as in surgical scars. In some cases lesions contain small pustules.

General phenotypes of psoriasis are chronic plaque, guttate, localized pustular, generalized pustular, and erythroderma.¹ Chronic plaque and guttate psoriasis are the most common, and generalized pustular psoriasis and erythroderma typically the most disabling and even life threatening. Chronic plaque psoriasis lesions are often relatively large in diameter and occur preferentially on elbows, knees, scalp, genitalia, lower back, and the gluteal cleft, although they may occur at many other locations. It is quite common for only one area of skin such as the scalp to be affected. Guttate lesions are relatively small in diameter and usually quite numerous, distributed preferentially on the trunk and proximal extremities (Figure 43-1). Guttate psoriasis occurs relatively commonly in children and young adults, often manifesting a few weeks after a streptococcal infection.

Figure 43-1 Guttate psoriasis resembles “drops” of discrete scaly papules with erythema, often on the trunk.

(Courtesy Dr. Nicole Rogers, Tulane University Department of Dermatology, New Orleans.)

Nail changes are common, occurring in about half of patients, and are often mistaken for fungal infection. Specific changes include pitting, onycholysis (“oil spots”), dystrophy of nails, and loss of the nail plate. These changes are not specific for psoriasis. Notably, pitting may occur as a result of trauma, and the finding of a few pits in the nails may not be helpful diagnostically. Nail changes are more frequent in patients with arthritis of the distal interphalangeal joints.²

Arthritis occurs more often in patients with severe cutaneous disease, but cutaneous disease need not be present at all. Remissions and exacerbations of arthritis do not correlate well with remissions and exacerbations of skin disease. The presence of psoriatic skin lesions may be helpful in supporting a diagnosis of psoriatic arthritis, although many patients with psoriasis have joint disease unrelated to psoriasis.

The diagnosis of psoriatic skin disease is usually made on clinical grounds alone, largely on the basis of the morphology and distribution of lesions. The differential diagnosis may be extensive and includes in selected cases nummular eczema, seborrheic dermatitis, candidiasis (in intertriginous areas), pityriasis rubra pilaris, Bowen’s disease or Paget’s disease (for isolated plaques), drug eruption, pityriasis rosea, pityriasis lichenoides, dermatophytosis, lichen planus, secondary syphilis, parapsoriasis, cutaneous lupus (especially subacute cutaneous lupus erythematosus [SCLE]), and dermatomyositis. In cases where the diagnosis is not clear-cut, biopsy may be helpful. The histologic findings may range from virtually diagnostic for psoriasis to merely consistent with but not diagnostic. Histologically, psoriasis cannot generally be distinguished from the skin lesions seen in reactive arthritis.

Common topical therapies include corticosteroids, tar, anthralin, calcipotriene, and tazarotene.³ Phototherapy using sunlight, broadband ultraviolet B (UVB), narrowband UVB, or psoralen ultraviolet A-range (PUVA) is still a mainstay of therapy for many patients. Common systemic therapies include methotrexate, acitretin, cyclosporine, and the relatively new biologic agents such as etanercept, adalimumab, infliximab, and ustekinumab. Cyclosporine may be useful to attain relatively rapid control of severe psoriasis, but it is less often used as a long-term therapy. Although topical corticosteroids are an acceptable treatment for many patients, systemic corticosteroids are avoided for the treatment of cutaneous disease, in particular due to the observation of severe flaring of psoriasis following withdrawal of systemic corticosteroids.

Reactive Arthritis

The diagnosis of reactive arthritis may be rather straightforward in a young male who develops urethritis, conjunctivitis, and arthritis following an episode of nongonococcal urethritis. However, in many cases the clinical features are not fully expressed and cutaneous lesions may be helpful in establishing the diagnosis.⁴

Circinate balanitis is the most common of the characteristic mucocutaneous lesions. Small erythematous papules and pustules coalesce to form serpiginous erosive or crusted plaques on the glans penis. In uncircumcised men, the appearance is more often that of erosion rather than crust because the moisture and trauma minimize the formation of crust. In circumcised men, crusting may be more obvious than erosion.

The palms and, particularly, the soles may develop lesions that are initially similar to the small erythematous papules and pustules of the genital region. With time, these lesions, termed keratoderma blenorrhagica, tend to become markedly hyperkeratotic (Figure 43-2). They may coalesce into large plaques or generalized hyperkeratosis involving the entire plantar surface, or they may remain discrete, erythematous, hyperkeratotic papules a few millimeters in diameter.

Figure 43-2 Reactive arthritis with keratoderma blennorrhagica of the feet.

Erythematous, scaly plaques indistinguishable from psoriasis may appear elsewhere on the skin including the scalp, elbows, and knees. When lesions occur around the nails, it is common for there to be hyperkeratosis underneath the nails. Pitting is not typical of reactive arthritis, but thickening, ridging, or shedding of the nail plate may occur. Erosions of the oral mucosa are relatively common on the tongue, buccal mucosa, and palate.

The diagnosis of the cutaneous lesions is usually made on a clinical basis. Skin biopsy may be helpful in excluding many entities in the differential diagnosis but generally cannot exclude psoriasis. Unfortunately, the major condition in the differential diagnosis of the skin lesions is usually psoriasis. One somewhat distinguishing histologic feature is that the older lesions of keratoderma blenorrhagica may have a considerably thickened stratum corneum, corresponding to the markedly hyperkeratotic papules seen grossly.

For the genital lesions, conditions to consider in the differential diagnosis may include candidiasis, psoriasis, dermatitis, Bowen’s disease, Paget’s disease, squamous cell carcinoma, Zoon’s balanitis, erosive lichen planus, lichen sclerosus (balanitis xerotica obliterans), aphthosis, fixed drug eruption, and certain infectious diseases. The differential diagnosis for lesions on the soles and palms may include psoriasis, hereditary or acquired hyperkeratosis of the palms and soles, pustular eruption of the palms and soles, pompholyx, scabies, and dermatophytosis. The differential diagnosis for oral lesions may include geographic tongue, lichen planus, candidiasis, aphthae, and autoimmune bullous diseases.

The approach to treatment of skin lesions is similar to that for psoriasis, particularly in cases where the lesions are persistent. Choice of topical therapies may be somewhat limited due to the sites involved. The oral mucosa is a difficult site to deliver medication topically, and the genital area may develop irritant reactions to certain topical medications. Often, topical corticosteroids are preferred for both areas because of low potential for irritation and the availability of topical preparations designed for these sites. In the genital area, suprainfection with Candida may occur and concurrent therapy with a topical or systemic anticandidal medication may be necessary on occasion.

Rheumatoid Arthritis

The major skin manifestations associated with rheumatoid arthritis (RA) generally fall under granulomatous lesions, exemplified by the rheumatoid nodule, and neutrophilic lesions, exemplified by vasculitis and pyoderma gangrenosum.

Rheumatoid nodules are the most common cutaneous manifestations of RA.⁵ They occur more often in seropositive patients and correlate somewhat with higher rheumatoid factor titers, more severe arthritis, and increased risk for vasculitis. Nodules are usually relatively deep, firm, and painless and tend to develop over areas of pressure and trauma such as the extensor forearms, fingers, olecranon processes, ischial tuberosities, sacrum, knees, heels, and posterior scalp (Figure 43-3). In patients who wear glasses, nodules may develop under the bridge or nosepieces. In most cases, rheumatoid nodules are in the subcutaneous tissue and/or deep dermis, but occasionally they may occur more deeply or more superficially.

Figure 43-3 Rheumatoid nodule over the extensor tendon of the distal interphalangeal joint.

Clinically, depending on the presentation, numerous entities may be in the differential diagnosis including infections, inflammatory disorders, and benign tumors. If needed, biopsy of a nodule may be quite helpful in establishing the diagnosis. Rheumatoid nodules exhibit a distinctive histologic finding called necrobiosis, a fibrinoid degeneration of the connective tissue, surrounded by palisaded histiocytes. Necrobiosis is also a characteristic feature of granuloma annulare and necrobiosis lipoidica diabeticorum. Although necrobiosis lipoidica diabeticorum is easily distinguished from rheumatoid nodule clinically, the subcutaneous variant of granuloma annulare may be difficult to distinguish, both clinically and histologically.

The term rheumatoid nodulosis has been used to describe an entity characterized by subcutaneous rheumatoid nodules, cystic bone lesions, rheumatoid factor positivity, and arthralgias in patients with little or no evidence of systemic manifestations of RA or erosive joint disease.⁶ Older males are preferentially affected.

The development of nodules in RA patients undergoing treatment with methotrexate has been noted by several observers and termed accelerated rheumatoid nodulosis.⁷ The nodules are newly appearing and occur preferentially on the hands. There are also case reports of the phenomenon in RA patients treated with etanercept.

The other major type of cutaneous lesion associated with RA is neutrophil predominant. Rheumatoid vasculitis occurs more frequently in patients who are seropositive and have rheumatoid nodules, and it often occurs relatively late in the course of the disease.⁸ Vessels of any size may be affected. In the skin, vasculitis may appear as purpuric papules and macules, nodules, ulcerations, or infarcts. Bywaters’ lesions are periungual or digital pulp purpuric papules representing a small vessel vasculitis, but not necessarily associated with vasculitic lesions elsewhere.

The differential diagnosis of purpuric or petechial lesions may include stasis dermatitis, Schamberg’s purpura, platelet dysfunction, petechial drug eruptions, viral exanthems, emboli, thromboses, and sludging. Of these, Schamberg’s purpura, a relatively common condition unassociated with systemic disease, is probably the most frequently confused with small vessel vasculitis. Skin biopsy may be helpful in establishing the diagnosis of vasculitis, particularly if an early lesion is sampled, although rheumatoid vasculitis cannot be distinguished histologically from many other causes of small vessel vasculitis. Immunofluorescent examination of an early lesion may be helpful in ruling out IgA-predominant vasculitis. The differential diagnosis of ulcers and infarcts is extensive. Biopsy is often unrewarding because nonspecific changes present in established lesions may make interpretation difficult, but on occasion biopsy of ulcers or infarcts may result in a definitive diagnosis of vasculitis.

The neutrophilic dermatoses are a group of diseases inflammatory rather than infectious in origin, typified by pyoderma gangrenosum and Sweet’s syndrome. These conditions have been associated with a variety of extracutaneous diseases including RA. The classic pyoderma gangrenosum lesion is a rapidly appearing, large, destructive ulcer in which the border is undermined. The classic lesion of Sweet’s syndrome is an erythematous, edematous plaque with a surface often described as mammillated, pseudovesicular, or microvesicular. Clinical appearances intermediate between these two have been described. For pyoderma gangrenosum, the differential diagnosis is usually that of conditions causing leg ulcer, and the diagnosis is mainly clinical, with biopsy primarily serving to exclude some of the other entities under consideration. For Sweet’s syndrome, the differential diagnosis may include infections, halogenoderma, and other neutrophilic dermatoses. Biopsy often provides helpful supporting evidence. The mainstay of therapy for acute lesions of both conditions is systemic corticosteroids. For more persistent lesions, a variety of options may be considered, cyclosporine and infliximab being two of the more common. Colchicine or potassium iodide may be first-line therapies for Sweet’s syndrome, particularly in patients with infections or contraindications to corticosteroids.

The term rheumatoid neutrophilic dermatitis has been given to describe chronic, erythematous, urticarial-like plaques that occur primarily on the distal arms.⁹ Clinically and histologically, rheumatoid neutrophilic dermatitis is similar to Sweet’s syndrome and may be a variant of it.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) of connective tissue disease is an unusual condition or set of conditions for which consistent terminology is still evolving. As the name implies, the major bases for diagnosis of this entity are the histologic appearance and the occurrence in a patient with connective tissue disease, often RA.¹⁰ The clinical appearance ranges from erythematous or flesh-colored papules that appear primarily on fingers and elbows to erythematous or flesh-colored linear cords on the trunk. Some authors classify the latter as interstitial granulomatous dermatitis with cutaneous cords or interstitial granulomatous dermatitis with arthritis (IGDA). Treatment of PNGD and IGDA can be challenging. PNGD may respond to dapsone or sulfapyridine. IGDA can be treated with antimalarials or immunosuppressives, but because this is both a newly described and relatively infrequent condition, all evidence is based on case reports and small case series. Patients can progress to a severe deforming arthritis. In some cases, granuloma annulare and rheumatoid nodule may be in the differential diagnosis.

Juvenile Rheumatoid Arthritis/Still’s Disease

The majority of patients with classic Still’s disease manifest an exanthematous eruption coincident with daily fever spikes.¹¹ The lesions are evanescent, usually nonpruritic, erythematous macules occurring over the trunk, extremities, and face. The differential diagnosis includes viral exanthem, drug eruption, familial periodic fever syndromes, and rheumatic fever. It is not unusual for exanthems of any type to be more prominent during fevers, but it is not expected that viral exanthems and drug eruptions clear completely between fever spikes. However, it should be noted that the eruption of erythema infectiosum (fifth disease) due to parvovirus B19 may resolve completely but reappear when the skin temperature rises, as with warm baths or exercise. Adult-onset Still’s disease is also typified by an evanescent erythematous, sometimes salmon-colored eruption over the trunk and extremities, associated with high fever. Skin biopsy may be nonspecific. However, there has been a report of a unique histologic pattern consisting of dyskeratotic keratinocytes in the upper epidermis along with increased dermal mucin in adult-onset Still’s disease.¹² The frequency with which this histologic pattern is present in Still’s disease remains to be determined.

Subcutaneous nodules may develop in both juvenile-onset and adult-onset Still’s disease. The lesions tend to occur at the same sites of the body, as do rheumatoid nodules in RA, but histologically they appear similar to nodules of rheumatic fever.

Lupus Erythematosus

The skin is involved at some time in the course of disease in the majority of patients with lupus erythematosus (LE), and skin lesions may be important in establishing the diagnosis. Some skin lesions are highly likely to be associated with “systemic” (i.e., extracutaneous) disease, whereas others may or may not be associated with extracutaneous disease. The phenomenon of lupus skin lesions occurring in the absence of systemic disease has previously been termed discoid lupus by some. However, dermatologists use this term to denote a specific type of skin lesion, regardless of presence or absence of systemic disease. It is the latter meaning of discoid lupus to which we refer in this chapter.

Lupus-Specific Skin Lesions

James Gilliam classified cutaneous lesions as being specific or nonspecific for lupus, discoid lupus lesions being an example of the former and palpable purpura being an example of the latter.¹³ Although this division of lesions is useful, sometimes a lupus-specific lesion occurs in a patient whose primary autoimmune disease is something other than LE. For example, SCLE lesions may occur in patients whose primary condition is Sjögren’s syndrome, and discoid lesions may be seen in a variety of conditions such as mixed connective tissue disease. Many of the lupus-specific skin lesions can occur in patients who have no evidence of extracutaneous disease.

The characteristic morphologies of the various lupus-specific skin lesions are in large part a function of the depth and intensity of the inflammatory infiltrate, presence or absence of epidermal basal cell damage, involvement of hair follicles, abundance of dermal mucin, and tendency to scar. In practice, there may be some overlap of these features and there may be more than one type of lesion present in a given patient, making classification difficult. Because therapy for most of the lupus-specific lesions is similar, it is not always important to distinguish among the various types of lesions. However, it can be useful to identify conditions that are more likely to scar, in order to target more aggressive therapy, and to identify conditions that are highly likely or highly unlikely to be associated with systemic disease.

Acute cutaneous lupus (ACLE) lesions are typified by malar erythema, the classic butterfly rash (Figure 43-4). The inflammation tends to be superficial, with little propensity to scar. Precipitation or exacerbation of lesions by sun exposure is common, and lesions tend to be distributed on the sun-exposed face, neck, extensor arms, and dorsal hands, where the skin over the knuckles is relatively spared. Often the lesions are quite transient, but they may be persistent. When the face is severely affected, facial edema may be prominent. Oral lesions are often present concurrently. Acute eruptions with considerable focal basal cell damage can result in erythematous papules with dusky centers that clinically mimic erythema multiforme. The major importance of recognition of ACLE is its strong association with systemic disease. The differential diagnosis of malar rash may include several conditions. In some cases, the facial rash of ACLE may be difficult to distinguish from rosacea. Seborrheic dermatitis, atopic dermatitis, and photosensitive eruptions such as polymorphous light eruption and drug-induced photosensitivity may also be considered. Dermatomyositis may cause a photosensitive facial erythema with edema similar to ACLE, although the erythema tends to be more violaceous. Persistent lesions on the neck and arms may be indistinguishable from SCLE. Discoid lupus lesions occasionally appear in a butterfly distribution, where they can result in disfiguring scarring. Skin biopsy is usually not performed on malar erythema because of its transient character, the scar resulting from biopsy, and the availability of other means of establishing the diagnosis of SLE. If a biopsy is done, it should be noted that dermatomyositis and SCLE cannot be distinguished from ACLE by histology and also that skin biopsy findings are sometimes nonspecific.

Figure 43-4 Acute malar rash in a butterfly distribution in systemic lupus erythematosus.

SCLE is a photosensitive eruption usually associated with anti-Ro/SSA autoantibodies.¹⁴ Lesional morphology is of two main types, annular erythematous plaques and scaly erythematous psoriatic plaques. Lesions are distributed over sun-exposed skin of the arms, upper trunk, neck, and sides of the face (Figure 43-5). Inexplicably, the midfacial area is usually uninvolved. Fair-skinned individuals are preferentially affected. Lesions may resolve with hypopigmentation or even depigmentation, but they rarely scar. Several drugs, particularly hydrochlorothiazide, have been reported to induce SCLE.¹⁵ The risk for development of systemic disease is not fully known, but perhaps 15% or so of patients with SCLE have or will develop significant systemic disease, often SLE, Sjögren’s syndrome, or an overlap. Depending on the morphology of the lesions and the clinical presentation, the differential diagnosis may include psoriasis, tinea, polymorphous light eruption, reactive erythema, and erythema multiforme. Skin biopsy for routine histology is often helpful in establishing the diagnosis. The characteristic finding of skin biopsy for immunofluorescence is a particulate deposition of immunoglobulin G (IgG) in the epidermis (Figure 43-6) both in lesions and uninvolved skin.¹⁶ This pattern can be reproduced in animal models by infusing anti-Ro, and thus immunofluorescence results provide information that duplicates serologic testing for anti-Ro.¹⁷ The particulate epidermal pattern seen in normal skin does not carry the same implication for increased risk of having SLE, as does the finding of granular deposits of IgG at the dermal-epidermal junction (the nonlesional lupus band test). It should be noted that many immunofluorescence laboratories do not routinely report epidermal findings.

Figure 43-5 Subacute cutaneous lupus erythematosus: annular-polycyclic type.

Figure 43-6 Direct immunofluorescence (lupus band test).

Discoid lupus erythematosus (DLE) lesions are the most common of the persistent lupus-specific skin lesions. Active lesions are erythematous papules and plaques that feel indurated to palpation because of the substantial numbers of inflammatory cells infiltrating the dermis. Involvement of hair follicles may be grossly evident as follicular plugs and scarring alopecia. Dyspigmentation is common, often with hypopigmentation or even depigmentation in the center and hyperpigmentation at the periphery (Figure 43-7). Visible scale is common and occasionally is pronounced in a clinical variant called hypertrophic DLE. In established lesions, scarring may be disfiguring. Lesions tend to occur on the scalp, ears, and face but may be widespread and occasionally involve mucosal surfaces. It is unusual to have lesions below the neck in the absence of lesions above the neck.¹⁸ Sun exposure may exacerbate DLE in some cases, but the presence of lesions in sun-protected areas of the scalp and ears and the frequent absence of a history of photosensitivity indicates that sun exposure is probably not a trigger in every instance. There are case reports of squamous cell carcinoma developing in established DLE lesions. In a patient who presents with DLE lesions, the risk for developing SLE is probably about 5% to 10%, although mild systemic symptoms such as arthralgias are relatively common. The differential diagnosis of DLE lesions is often that of conditions exhibiting intense lymphocytic or granulomatous infiltrates such as sarcoid, Jessner’s lymphocytic infiltrate, granuloma faciale, polymorphous light eruption, lymphocytoma cutis, and lymphoma cutis. In the scalp, lichen planopilaris and other scarring alopecias may be considered. Skin biopsy for routine histology often establishes the diagnosis definitively. In more difficult cases, biopsy for immunofluorescence may provide additional supporting diagnostic information. Lesions are expected to have granular deposits of immunoglobulins at the dermal-epidermal junction. Unless there is concomitant systemic disease, normal skin is expected not to have immunoglobulin deposits.

Figure 43-7 Discoid lupus erythematosus of the scalp, with scarring alopecia and central hypopigmentation.

(Courtesy Dr. Nicole Rogers, Tulane University School of Medicine, New Orleans.)

Tumid lupus (TLE) skin lesions are similar to DLE lesions in that they are erythematous indurated papules and plaques with a substantial lymphocytic infiltrate. Unlike DLE, though, the lesions do not exhibit epidermal abnormalities, follicular involvement, or scarring. Considerable mucin is present in the dermis, giving the lesions a somewhat boggy look and feel. In some reports, lesions are most common on the face and may be reproduced by phototesting.¹⁹ The risk for SLE appears to be low, and immunoglobulin deposits are not generally present in skin biopsies. Jessner’s lymphocytic infiltrate and other lymphocytic and granulomatous infiltrative conditions (see earlier) are in the differential diagnosis. Skin biopsy for routine histology is valuable in establishing the diagnosis, with the exception of reliably distinguishing TLE from Jessner’s lymphocytic infiltrate. Some have argued that Jessner’s lymphocytic infiltrate and TLE are one and the same, and it might reasonably be argued that what is called TLE is not appropriately classed as a form of chronic cutaneous LE but rather as an independent entity. However, the presence of TLE lesions in some patients with lupus is evidence to the contrary.

Lupus panniculitis (LEP) lesions have inflammation in the subcutaneous tissue, resulting in deep indurated plaques that become disfiguring, depressed areas (Figure 43-8). Usual sites of involvement are face, upper trunk, breasts, upper arms, buttocks, and thighs. The risk for SLE is not known precisely, but clearly some patients with LEP have or will develop SLE. The differential diagnosis is that of the panniculitides, but the distribution exhibited in LEP is unusual for most other conditions that cause panniculitis. The combination of clinical presentation and skin biopsy for histology usually serves to establish the diagnosis.

Figure 43-8 Lupus profundus (panniculitis) with extensive atrophy.

Some unusual variants of cutaneous lupus are chilblain lupus (red or dusky plaques on colder areas of skin such as fingers, toes, nose, elbows, knees, and lower legs), cutaneous lupus/lichen planus overlap, and a bullous eruption due to autoantibodies to type VII collagen or other basement membrane zone proteins. Not all bullae related to lupus are due to autoantibodies to basement membrane proteins, however. It is not unusual to develop bullae simply from intensive destruction of the basal cell layer in ACLE, SCLE, or, rarely, DLE.

Treatment of the lupus-specific lesions is relatively similar for most of the subtypes, with some exceptions and modifications. Sun protection is critical for lesions that are initiated or exacerbated by sun exposure. Many or most patients underestimate the amount of sunscreen needed to apply, the potential damage of the seemingly minimal exposure one has in the course of day-to-day activities, and the value of protective clothing. Topical therapy is often used to avoid side effects of systemic medications or to provide adjunctive therapy, although topical agents are unlikely to be beneficial if the disease process is deep, as in panniculitis. Topical or intralesional corticosteroids are the most often used local therapy, but there are some reports of benefit from topical calcineurin inhibitors and topical retinoids.^20,²¹ The first-line systemic medication for cutaneous lupus is antimalarial therapy. Several reports indicate that smoking tobacco decreases the likelihood of response to antimalarials.²² For antimalarial-resistant skin disease, a wide variety of medications have been used but there is no clear second choice when antimalarials have not worked. Although dapsone is arguably not helpful in most types of cutaneous lupus, it may be helpful in neutrophil-predominant bullous eruptions.²³ Measures to keep the skin warm may be useful for chilblains lupus.

Nonspecific Cutaneous Lesions

A wide variety of lupus nonspecific skin lesions has been reported. Many of these such as vasculitic lesions are cutaneous clues to the possibility of extracutaneous disease. Noteworthy in this regard is livedo reticularis. The netlike erythema of livedo reticularis is a vascular phenomenon due to lowered oxygenation at the periphery of the area supplied by a particular vessel. This can simply be due to vasoconstriction, such as occurs in a cold environment, and thus can be a benign finding. If livedo is more prominent than usual, not corrected by warming, and persistent, it can indicate lowered flow due to pathology such as vasculitis, atherosclerotic disease, or sludging. In lupus, livedo reticularis may be a sign of the presence of antiphospholipid antibodies.²⁴

Other lupus nonspecific skin lesions include Raynaud’s phenomenon, palmar erythema, periungual telangiectasia, alopecia, erythromelalgia, papulonodular mucinosis, and anetoderma. Sclerodactyly, calcinosis, and rheumatoid nodules have been reported but may be more likely in overlap syndromes than in SLE.

Neonatal Lupus Syndrome

Neonatal lupus erythematosus (NLE) is associated with maternal IgG autoantibodies to Ro/SSA and La/SSB.²⁵ Affected children may have cutaneous lesions, cardiac disease (notably complete heart block and/or cardiomyopathy), hepatobiliary disease, or hematologic cytopenias. Most children have only one or two features of the disease. Similar to the anti-Ro/SSA-associated SCLE of adults, the skin lesions are often photosensitive, have relatively superficial inflammatory infiltrates, and do not tend to scar. The lesions usually appear at a few weeks of age but have been noted at birth in several cases. The natural history of the skin disease is that the lesions last for weeks or months and resolve spontaneously, usually leaving no residuum. In a few cases, persistent telangiectasias have been noted. Individual lesions appear as erythematous annular papules or plaques. Lesions are usually more numerous and more intensely inflamed on the face and scalp but may additionally occur on the trunk and extremities. Confluent periorbital erythema, giving the appearance of an erythematous mask, is common and diagnostically helpful. Even though the skin disease resolves and most children without extracutaneous involvement remain otherwise healthy, there is a possibility that children who have had NLE are at increased risk for the development of autoimmune disease later in childhood.²⁶

Differential diagnosis of the skin lesions may include reactive erythema, drug eruption, erythema multiforme, and urticaria. Annular NLE lesions usually have little or no scale, unlike the annular lesions of tinea. In areas where there is intense destruction of the basal cell layer, lesions may be crusted and look similar to bullous impetigo. Treatment of skin lesions consists largely of sun protection and mild topical steroids.

The pathogenesis of lupus is covered elsewhere, but it is noteworthy that SCLE-like, anti-Ro/SSA-associated skin lesions may occur in neonates, but other lupus-specific skin lesions do not appear to be maternally transmissible.

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