What Are These Annular, Polycyclic Plaques?

A 5-year-old Asian boy presented with a 6-month history of a rash on his arms. The child was born at term to a healthy 25-year-old primigravida, and his parents were nonconsanguineous. The boy met all his developmental milestones and was not taking any medications. The family history was unremarkable for cutaneous or autoimmune disorders. According to his mother, the rash was exacerbated in the summer. The child was asymptomatic and was otherwise in good health. 

 Physical examination revealed a well-appearing child with multiple, erythematous annular, polycyclic, slightly scaling plaques symmetrically distributed on his arms. No mucosal lesions were evident. The rest of the physical examination results were unremarkable. 

Laboratory investigation results showed that the antinuclear antibodies (ANA) were positive at a titer of 1:640 with a speckled pattern, and the anti-Ro (SSA) antibodies were positive at a titer of 160. The erythrocyte sedimentation rate was slightly elevated at 15 mm/h (normal, < 10 mm/h). Anti-DNA, anti-La (SSB), anti-Smith, and anti-ribonucleic protein antibodies were not detected. The results of other investigations, including urinalysis, complete blood cell count, liver function tests, renal function tests, serum complements, and serum immunoglobulins, were all unremarkable.

Results of a histopathologic examination of a skin biopsy from a representative lesion showed orthohyperkeratosis, epidermal atrophy, basal cell vacuolation, papillary edema, perivascular and periadnexal lymphocytic infiltrate in the upper and middle dermis, and dermal mucin deposition. 

What’s your diagnosis?

(Answer and discussion on next page)

ANSWER: Subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus is a distinct subset of cutaneous lupus erythematosus, clinically characterized by nonscarring, nonatrophic, erythematous, papulosquamous or annular polycyclic lesions in sun-exposed areas, often associated with anti-Ro/SSA antibodies.¹ The condition was first defined as a distinct clinical entity, and the term “SCLE” was coined by Sontheimer et al in 1979.² Other subtypes include acute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus. 

EPIDEMIOLOGY 

The overall incidence of SCLE has been estimated at 0.6 per 100,000 persons.^3,4 The male to female ratio is approximately 1:4, except in the drug-induced form, in which the sex ratio is equal.^5-7 The mean age of onset is in the third to fourth decade, although children can also be affected.^6-8 In addition, the condition is more commonly reported in Caucasian patients.³

ETIOPATHOGENESIS

The pathogenesis is multifactorial; immunologic, genetic, and environmental factors play an important role in the pathogenesis of the disease. SCLE is considered an autoimmune disorder resulting from the development of autoimmunity directed specifically at nucleosomes and ribonucleotides.⁸ The majority of affected patients have anti-Ro/SSA antibodies (70% to 90%) and ANA (60% to 80%).^1,7 Anti-La/SSB antibodies are present in 35% of patients.⁸ SCLE occurs more often in patients with other autoimmune disorders such as rheumatoid arthritis and Sjögren syndrome.

There is also a genetic predisposition. The condition is more common in patients with human leukocyte antigen (HLA)-A1, HLA-B8, HLA-DR3, HLA-DRw52, and HLA-DQ1.^6,8 Other genes outside the major histocompatibility complex region, such as interleukin-1 receptor antagonist and tumor necrosis factor α promoter gene polymorphisms have also been implicated in the pathogenesis of SCLE.^6-9 In addition, deficiencies of C2 and C4 components of complement have been associated with both SCLE and systemic lupus erythematosus (SLE).⁷

Approximately one-third of cases are drug-induced.^4,10 Although anti-histone antibodies are strongly associated with drug-induced SLE, they are positive in only one-third of drug-induced SCLE cases.¹¹ Medications that have been reported to induce SCLE are outlined in the accompanying Table.^4,9,12  

Ultraviolet light plays a pivotal role; SCLE lesions are characteristically photodistributed. Other triggering factors include smoking, viral infections, and radiotherapy.¹³ Rarely, SCLE may arise as a paraneoplastic phenomenon.¹⁴

HISTOPATHOLOGY

Histopathologic findings include orthohyperkeratosis, epidermal atrophy, dermal edema, vacuolar degeneration of the basal cell layer, and perivascular lymphocytic infiltrate.⁸

CLINICAL MANIFESTATIONS 

SCLE typically presents with erythematous, slightly scaly papules that evolve into annular and/or psoriasiform plaques.⁸ The former often coalesce to form polycyclic or figurative  patterns with raised red borders and central clearing.⁹ Although annular and psoriasiform plaques may coexist, most patients exhibit one predominant type of lesion. SCLE lesions are characteristically photodistributed; sites of predilection include the neck, shoulders, upper extremities, and upper trunk, but not the face.⁹ Lesions are usually widespread, symmetrical, and not pruritic. Hypopigmentation and telangiectases may occur, most commonly at the center of the lesion.¹⁵ Other cutaneous lesions that may occur include oral mucous membrane lesions, nonscarring alopecia, livedo reticularis, periungual telangiectases, and Raynaud phenomenon.¹ Patients with drug-induced SCLE may have malar erythema, bullous lesions, targetoid lesions, vasculitic lesions, and widespread disease.¹²

It is not unusual for affected patients to have musculoskeletal symptoms, such as arthralgia and fatigue.^8,15 Arthritis is unusual. Systemic disease, if present, is usually mild.¹ Although a subset of patients with SCLE will meet the American College of Rheumatology criteria for a diagnosis of SLE, most patients do so based on laboratory and mucocutaneous criteria.¹⁶ As such, these criteria cannot be used to distinguish SCLE patients with significant systemic disease from those without.¹⁶

SCLE lesions usually heal without scarring or dermal atrophy.^1,9 However, they may leave residual dyspigmentation.

LABORATORY INVESTIGATIONS

Laboratory investigations should be individualized, based on the level of confidence in making the diagnosis and the suspicion of systemic involvement. The following tests may be considered: urinalysis, complete blood cell count, blood urea nitrogen, serum creatinine, serum complements (C3 and C4), ANA, anti-Ro/SSA antibodies, anti-La (SSB) antibodies, anti-DNA antibodies, anti-histone antibodies, anti-Smith antibodies, and anti-ribonucleic protein antibodies.¹¹

DIAGNOSIS 

The diagnosis should be suspected in patients with annular or papulosquamous eruptions in sun-exposed areas that are not followed by scarring or dermal atrophy, high association with anti-Ro/SSA antibodies and ANA, and lack of significant systemic involvement.¹³ The diagnosis is often confirmed with a skin biopsy and/or referral to a dermatologist.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis includes discoid lupus erythematosus, neonatal lupus erythematosus, lupus erythematosus tumidus, lupus erythematosus profundus, tinea corporis, atopic dermatitis, nummular eczema, chronic urticaria, drug-related eruptions, dermatomyositis, psoriasis vulgaris, polymorphous light eruption, seborrheic dermatitis, erythema annulare centrifugum, and pityriasis rubra pilaris.^7,8,17

PROGNOSIS

Generally, the prognosis is good. Some patients have spontaneous remission, but others may run a recurring and remitting course.¹⁵ A subset of patients will progress to active SLE; these patients often have high ANA and anti-Ro/SSA titers.⁸

MANAGEMENT 

Preventative measures include elimination/avoidance of provoking factors. Measures that should be emphasized are avoiding sun exposure, especially during hours of peak ultraviolet intensity (11:00 am to 4:00 pm); regularly using broad-spectrum sunscreens; and wearing protective clothes when outdoors. Any offending medications should be discontinued. Most patients experience improvement within 8 weeks after the offending medication has been discontinued.⁶ In addition, cessation of smoking is essential. 

Topical corticosteroids are the drugs of choice.⁹ Intralesional corticosteroids may be considered for small and thicker lesions.⁹ Topical calcineurin inhibitors can also be used. More severe disease warrants treatment with antimalarial agents, in particular, hydroxychloroquine. For recalcitrant cases, there are several treatment options, including systemic corticosteroids, oral retinoids, and immunosuppressive agents (eg, methotrexate, azathioprine, cyclosporine, and cyclophosphamide).¹⁸n

Alexander K. C. Leung, MD, is a Clinical Professor of Pediatrics at the University of Calgary and a pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada.

Benjamin Barankin, MD, is a dermatologist and the Medical Director and Founder of the Toronto Dermatology Centre in Toronto, Ontario, Canada.

REFERENCES 

1. Amato L, Coronella G, Berti S, et al. Subacute cutaneous lupus erythematosus in childhood. Pediatr Dermatol. 2003;20(1):31-34.

2. Sontheimer RD, Thomas JR, Gilliam JN. Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol. 1979;115(12):1409-1415.

3. Durosano O, Davis MD, Reed KB, Rohlinger AL. Incidence of cutaneous lupus erythematosus, 1965-2005: a population-based study. Arch Dermatol. 2009;145(3):249-253.

4. Gronhagen CM, Fored CM, Linder M,  Granath F, Nyberg F. Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden. Br J Dermatol. 2012;167(2):296-305. 

5. Ciconte A, Mills AE, Shipley A, Marks R. Subacute cutaneous lupus erythematosus presenting in a child. Australas J Dermatol. 2002;43(1):62-64.

6. Miller KK, Chiu J, Patel R, Kamino H. Drug-induced subacute cutaneous lupus erythematosus related to doxycycline. Dermatol Online J. 2011;17(10):3.

7. Stavropoulos PG, Goules AV, Avgerinou G, et al. Pathogenesis of subacute cutaneous lupus erythematosus. J Eur Acad Dermatol Venereol. 2008;22(11):1281-1289.

8. Berry T, Walsh E, Berry R, DeSantis E, Smidt AC. Subacute cutaneous lupus erythematosus presenting in childhood: a case report and review of the literature. Pediatr Dermatol. 2014;31(3):368-372.

9. Schur PH, Moschella SL. Mucocutaneous manifestations of systemic lupus erythematosus. In: Post TW, ed. UpToDate. http://www.uptodate.com/contents/mucocutaneous-manifestations-of-systemic-lupus-erythematosus. Updated April 16, 2014. Accessed April 1, 2016.

10. Callen JP. Consider drugs as a cause or an exacerbating factor in patients diagnosed with subacute cutaneous lupus erythematosus. Br J Dermatol. 2012;167(2):227-228.

11. Lowe G, Henderson CL, Grau RH, et al. A systematic review of drug-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2011;164(3):465-472.

12. Wilkerson E, Hazey MA, Bahrami S, Callen JP. Golimumab-exacerbated subacute cutaneous lupus erythematosus. Arch Dermatol. 2012;148(10):1186-1190.

13. Kolm I, Pawlik E, Eggmann N, et al. Subacute cutaneous lupus erythematosus triggered by radiotherapy. Case Rep Dermatol. 2013;5:232-235.

14. Evans KG, Heymann WR. Paraneoplastic subacute cutaneous lupus erythematosus: an underrecognized entity. Cutis. 2013;91(1):25-29.

15. Schoch JJ, Peters MS, Reed AM, Tollefson MM. Pediatric subacute cutaneous lupus erythematosus: report of three cases. Int J Dermatol. 2015;54(5):e169-e174.

16. Tiao J, Feng R, Carr K, Okawa J, Werth VP. Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE). J Am Acad Dermatol. 2016;74(5):862-869.

17. Hon KL, Leung AK. Neonatal lupus erythematosus. Autoimmune Dis. 2012;2012:301274.

18. D’Erme AM, Milanesi N, Difonzo EM, Lotti T, Gola M. Treatment of refractory subacute cutaneous lupus erythematosus with oral isotretinoin: a valid therapeutic option. Dermatol Ther. 2012;25(3):281-282.