Autoimmune Connective Tissue Diseases

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Discuss the skin changes of lupus erythematosus

Skin changes occur in about 855 of patients with lupus erythematosus (LE) and in this condition are second in frequency only to musculoskeletal complaints. Skin eruptions in LE may be categorized based upon diagnostic and prognostic significance. Skin lesions diagnostic of LE are called “lupus-specific eruptions.” On biopsy, such lesions show characteristic histopathologic changes of cutaneous LE. In fact, it may be possible to subclassify the type of lupus present (discoid, tumid, subcutaneous, etc.) based upon the findings of a cutaneous biopsy.

However, lupus patients may also develop nonspecific skin changes ( Table 22.1 ). These types of eruptions do not establish a diagnosis of LE but may have value in making an overall assessment of the connective tissue disease. For example, palpable purpura occurring in a patient with LE are not disease specific, as such lesions may occur in those without LE, yet the finding may point to concern for lupus-associated vasculitic disease of the kidney or central nervous system (CNS), and these data may be important in evaluation and management of the patient.

Kuhn A, Landmann A. The classification and diagnosis of cutaneous lupus erythematosus. J Autoimmun. 2014;49:14–19.

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What is acute cutaneous lupus erythematosus (ACLE)?

ACLE presents as an acute malar rash or a more generalized photodistributed eruption. The term “butterfly rash” is used to characterize the malar rash because the rash upon the cheeks resembles the wings of a butterfly ( Fig. 22.1 ). Nearly all patients presenting with ACLE will have systemic LE (SLE), often with an acute exacerbation. ACLE is typically transient, and it improves with the SLE improves, and it does not usually result in scarring.

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Are there other common skin eruptions that can be confused with ACLE?

The differential diagnosis for erythematous conditions of the face includes rosacea, polymorphous light eruption, photoreactions to systemic medications or topical products, seborrheic dermatitis, tinea faciei, and certain types of porphyria (see Chapter 17 ). Rosacea can closely mimic ACLE, particularly for persons new to dermatology. Rosacea is both common and typically photoexacerbated. Additionally, nonspecific joint complaints are common, and 5% of the normal population will have a positive antinuclear antibody (ANA) test, and this can lead to misdiagnosis of ACLE. Remember, a patient with ACLE is most often experiencing an acute flare and will be “ill,” whereas a rosacea patient will not typically be acute unwell. Also, seborrheic dermatitis is ubiquitous but often presents with waxy yellow scaling, erythema, and pruritus in the scalp, in the eyebrows, in the nasolabial folds, and the periauricular areas. Patients with seborrheic dermatitis are also not generally ill-appearing.

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What is subacute cutaneous LE (SCLE)?

SCLE was first described and characterized in the late 1970s. Patients with SCLE have an eruption that is more persistent than that of ACLE, lasting weeks to months. The condition is most common in middle-aged white women. Lesions of SCLE consist of scaly, superficial, inflammatory macules, patches, papules, and plaques that are photodistributed, particularly on the upper chest and back, lateral neck, and dorsal arms and forearms. Several different morphologic types of SCLE have been described: annular, serpiginous, psoriasiform, and pityriasiform ( Fig. 22.2 ). Some patients have lesions with more than one morphology. Nearly all patients with SCLE manifest anti-SSA (Ro) antibodies.

Many patients with SCLE will have four or more criteria for the classification of SLE, although most SCLE patients do not have serious renal or CNS LE. Typically, they have skin disease, photosensitivity, and musculoskeletal complaints. Dry eyes and dry mouth are also common. Some patients with SCLE experience severe manifestations of SLE, and thus, all SCLE patients should be monitored for systemic disease.

Alniemi DT, Gutierrez A, Drage LA, et al. Subacute cutaneous lupus erythematosus: clinical characteristics, disease associations, treatments, and outcomes in a series of 90 patients at Mayo Clinic, 1996–2011. Mayo Clinic Proc . 2017;92:406–414.

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How do you make a diagnosis of SCLE?

SCLE is often diagnosed based upon a typical photodistributed eruption and a skin biopsy consistent with cutaneous LE. In further support of the diagnosis, nearly all patients with SCLE have anti-SSA (Ro) antibodies and less often anti-SSB (La) antibodies. Direct immunofluorescence studies show granular deposition of immunoreactants at the dermoepidermal junction or particulate-like deposition in the lower epidermis. Such antibodies are not present in all patients with SCLE, and hence, the absence of these findings does not exclude this diagnosis. Additionally, a negative ANA does not exclude the diagnosis of SCLE, for some patients will have anti-SSA (Ro) in isolation.

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What is the initial workup of SCLE?

Once a diagnosis of SCLE is made, it is important to evaluate for the presence of SLE:

• History and physical exam data should be culled to identify manifestations of SLE in other organ systems

• Laboratory testing will often include a complete blood count with differential, urinalysis, basic serum chemistries (including renal function tests), liver function studies, and an ANA panel to include anti-SSA (Ro), anti-SSB (La), and anti-DNA antibodies. Complement determinations may be ordered, as some SCLE patients have partial or complete complement deficiencies

• An increased risk of cancer has been associated with SCLE, so appropriate screening for various internal cancers such as breast cancer, lymphoma, respiratory cancer, and nonmelanoma skin cancer should be performed

• A medication history is important, since SCLE may be triggered or worsened by a number of medications, especially thiazide diuretics, tumor necrosis factor-α blockers, terbinafine, angiotensin-converting enzyme inhibitors, proton pump inhibitors, and antiepileptics, among others (see Table 22.2 ).

  Table 22.2

  Medications associated with subacute cutaneous lupus erythematosus

  Adalimumab Aldactone Captopril Cilazapril Cinnarizine Diltiazem Docetaxel Etanercept

  Glyburide Gold Griseofulvin Hydrochlorothiazide Infliximab Interferon-α, -β Leflunomide Naproxen

  Nifedipine Nitrendipine Omeprazole Oxprenolol Penicillamine Phenytoin Piroxicam Pravastatin

  Procainamide Ranitidine Simvastatin Spironolactone Sulfonylureas Taxotere Terbinafine Verapamil

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How is SCLE managed?

Cutaneous complaints are often of most concern to patients with SCLE, and hence, dermatologists are often the physicians managing the disease. Because the disease is driven the sunlight exposure, photoprotective measures, such as broad-spectrum sunscreens, protective clothing, and lifestyle modification are important measures. Cutaneous lesions may respond to potent topical steroids or topical calcineurin inhibitors. Often, oral antimalarial therapy is the most beneficial, but it has a slow onset. Other treatments less frequently employed include dapsone, retinoids, systemic steroids, methotrexate, mycophenolate, azathioprine, and rarely thalidomide, clofazamine, intravenous immune globulin, and rituximab.

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What is chronic cutaneous LE?

Several types of cutaneous LE that are persistent are termed chronic cutaneous LE . Discoid LE (DLE) is the most common of these chronic forms. DLE typically presents on the head and neck with thick keratotic scale and “triphasic” coloration. Scarring quickly results from DLE. Tumid LE has minimal scale and epidermal changes and consists chiefly of erythematous lesions caused by mucin accumulation in the underlying dermis. Lupus panniculitis and nodular cutaneous lupus mucinosis represent other forms of chronic cutaneous LE.

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Describe the skin changes of DLE

DLE consists of fixed, indurated, erythematous papules and plaques that are photodistributed and are particularly common on the head and neck, although any cutaneous region can be affected ( Fig. 22.3 A ). Without intervention, DLE lesions can last for years and may produce extensive scarring. When DLE involves the scalp, permanent scarring alopecia may result. Pigmentary changes (both hyperpigmentation and hypopigmentation) are often seen with DLE. Epidermal changes, including scale, keratotic plugging of the hair follicles, and sometimes crusting, are typically present. The external ears, and particularly the conchal bowls, are often involved in DLE ( Fig. 22.3 B), and this area always be examined in patients with suspected DLE.

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Do patients with DLE develop SLE?

If the initial workup of a patient with localized lesions of DLE does not reveal evidence of SLE, the risk of developing SLE is about 5%. If lesions are generalized, the risk of systemic disease may be slightly higher. However, DLE lesions are not uncommon in patients with a known diagnosis of SLE. About 25% of patients with SLE patients will develop DLE lesions in the course of their disease ( Table 22.3 ).

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