Erythematous papules and plaques


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Case #1

A 46-year-old white woman presents with a 2-week history of a rash on her back and feet. She denies any associated pain, pruritus, or fever, and her medical history is unremarkable. Her social and family histories are noncontributory. Physical examination is notable for erythematous papules scattered across her back, with some coalescing into plaques. Examination of her dorsal feet showed symmetrical, erythematous to skin-colored annular plaques that are 2 to 5 cm in diameter. The lesions do not exhibit tenderness or scaling. Her hands, nails, scalp, and face are normal.

Case #2

A 42-year-old white man presents with a 3-month history of rash on his back and chest. He denies having pruritus, but he complains of arthralgias and he has tried topical corticosteroids without experiencing improvement. His medical history is noncontributory. After a physical examination is conducted, the patient is observed to have multiple nonscaly, annular, pink to violaceous plaques on his back with swelling in the periphery and a flat center. His chest exhibits similar, smaller plaques and scattered pink papules. His scalp, hair, and nails are normal.

Case #1Granuloma annulare (GA) is a disorder of T cells and macrophages that presents most commonly in patients under age 30 with a female-to-male ratio of 2:1 in its most common, localized form.1 Generalized GA is more likely to occur...

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Case #1

Granuloma annulare (GA) is a disorder of T cells and macrophages that presents most commonly in patients under age 30 with a female-to-male ratio of 2:1 in its most common, localized form.1 Generalized GA is more likely to occur in patients of middle age or older and may have increased frequency in men. Another variant, subcutaneous GA, is more common in children.2

Although GA is a relatively common disease, its etiology remains unknown. Various inciting factors proposed in the literature include biologic therapies, various drugs, insect bites, trauma, Bacillus Calmette-Guérin vaccination, and herpes zoster infection.2 Associations of GA with systemic and infectious diseases, such as diabetes mellitus, malignancy, thyroid disease, dyslipidemia, human immunodeficiency virus (HIV), hepatitis B and C, and rheumatoid arthritis, have also been cited.2-6 

Based on the Th1 immune cells seen in the lesions, GA has been described a delayed-type hypersensitivity reaction to unknown antigens. This tuberculous-like immune response involves the production of interferon-γ and other cytokines that cause macrophage accumulation in the dermis and connective tissue degradation, such as elastic fiber degeneration and injury. Some studies reported genetic links and familial cases.1,2

GA is a benign, self-limited, and polymorphic cutaneous disease with many variants (localized, generalized, subcutaneous, and perforating). Subtypes of generalized GA include generalized annular, disseminated papular, and atypical generalized GA. The most commonly seen subtype is localized GA, in which annular erythematous or skin-colored papules present on the dorsal hands or feet; it makes up approximately three-quarters of all GA cases.2 Almost two-thirds of GA cases are isolated to the hands and arms, 20% to the legs and feet, 7% to both upper and lower extremities, 5% to the trunk, and 5% to the trunk plus other areas.1 Generalized GA is defined by at least 10 skin lesions present at once or by extensive annular plaques. Disseminated GA presents with a pattern of scattered papules. Atypical generalized GA fits neither the description of annular or disseminated GA. Subcutaneous GA presents most commonly on the lower legs and is also referred to as pseudorheumatoid nodules. Perforating GA papules have a clinically distinct central umbilication or keratotic plug due to collagen destruction. Rare subtypes include macular or patch type, palmar, photodistributed, and pustular GA. Although most GA lesions are asymptomatic, there are reports of pruritic and painful cases.1,2

GA has a broad differential diagnosis; therefore, skin biopsy is necessary for definitive diagnosis when suspected. The differential includes sarcoidosis, granulomatous mycosis fungoides, necrobiosis lipoidica, interstitial granulomatous dermatitis, tinea, nummular eczema, psoriasis, cutaneous lupus, leprosy, verruca vulgaris, and eruptive xanthomas. Subcutaneous GA can be clinically similar to rheumatoid nodules, sarcoidosis, and infectious processes.1,2 Clinical findings and histology together differentiate GA from the other diseases listed.

Histologically, palisading granulomas in the dermis with central degeneration of collagen, mucin, and an infiltrate of lymphocytes and histiocytes characterize GA. Mucin distinguishes GA from the other noninfectious granulomatous diseases. Sarcoidosis exhibits noncaseating granulomas without mucin. Necrobiosis lipoidica diffusely involves the dermis with granulomas in parallel layers and plasma cell infiltrates without mucin. Cutaneous lupus classically involves the dermal-epidermal junction with necrotic keratinocytes and no mucin. Lupus erythematosus tumidus, however, demonstrates a lymphocytic infiltrate confined to the dermis and contains mucin, but it does not exhibit the histiocytic infiltrate necessary for a diagnosis of GA. Perforating GA is unique in that it is characterized by collagen being ejected through the epidermis.1,2,7

Management of GA depends on the clinical characteristics. Localized and asymptomatic disease can be managed with reassurance and clinical observation. Patients with localized GA who are concerned about symptomatic lesions or cosmesis may benefit from first-line high-potency topical corticosteroids or intralesional corticosteroid injections. Topical tacrolimus 1% ointment, cryosurgery, localized psoralen with ultraviolet A light (PUVA) therapy, photodynamic therapy, and various lasers have also shown some success should corticosteroids fail.1,2

In their review, Thornsberry and English2 discussed more than 30 successful therapies cited in the literature for nonlocalized GA, but none are evidence-based. Systemic agents are often necessary for generalized GA. Isotretinoin at 0.5 to 1.0 mg/kg/d is most commonly used first. Intravenous use of infliximab, adalimumab, PUVA, cyclosporine, and doxycycline are other therapies that have shown success in case reports or case series. Combination therapies of PUVA with prednisone and isotretinoin with topical pimecrolimus 1% cream have also been effective.1,2,8

Half of all patients have resolution of GA within 2 years and have a 40% recurrence rate. Untreated GA has been documented to persist for several weeks to several decades.1 Given the association with various systemic diseases, a thorough review of systems is recommended, as is encouraging the patient to follow up with his or her primary care provider for any needed screening. Furthermore, therapy must be chosen taking into consideration the patient’s medical history, laboratory results, current medications, and potential for pregnancy given the various adverse side effect profiles and interactions of systemic agents.2

Regarding the patient in the vignette, a punch biopsy of a lesion on her back confirmed the diagnosis of GA. The patient was reassured that her lesions were benign and was prescribed clobetasol propionate 0.05% cream twice daily for 2 weeks on lesions of cosmetic concern. At 1-month follow-up, her lesions exhibited almost complete resolution.

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Case #2

Lupus erythematosus tumidus (LET) is classified as a variant of cutaneous lupus erythematosus (CLE), but there is debate as to whether it should be considered an independent entity. Although there are no reliable data regarding its incidence and prevalence, LET affects both men and women and is thought to be underdiagnosed. Most cases in the literature are reported in white subjects. The mean age of onset is in the 30s and 40s, but there are reports of affected children.1,9,10

Cutaneous lesions in lupus erythematosus (LE) are categorized into histopathologically specific and nonspecific subtypes. The CLE-specific lesions are further subcategorized as acute, subacute, or chronic. Acute CLE includes the transient, erythematous malar rash, diffuse alopecia, oral ulcers, plaques, and bullae often associated with systemic LE. Subacute CLE includes the inflammatory, scarring discoid lupus erythematosus (DLE), nonscarring photosensitive CLE, and psoriasiform lesions. LET is considered a form of chronic CLE, along with DLE, lupus panniculitis, and chilblain lupus, which are infrequently seen in systemic LE. However, the duration of the lesions may vary among patients.1 A newer classification of intermittent cutaneous LE was proposed for LET in 2004.9

LET typically presents as indurated plaques with a pink or violaceous hue and smooth surface in photodistributed areas, such as the face, upper back, neck, extensor surfaces, and shoulders. However, there are cases of LET in sun-protected areas of skin. LET lesions appear succulent or swollen with well-demarcated borders, and they do not show macroscopic epidermal involvement, such as follicular plugging or scale. The borders of the plaques may coalesce, leading to a raised periphery and relatively flatter center.9,11-14

Some patients have exhibited erythematous, annular lesions on the cheeks and upper extremities, resembling the annular subtype of subacute CLE, but they do not demonstrate the collarette scale seen in the subacute form.9 LET is further distinguished from other types of CLE by the absence of scarring, follicular plugging, and hyperkeratotic scaling, as is seen in DLE. Epidermal atrophy and postinflammatory hypopigmentation are also not seen in LET.9-14

Several reports have indicated specific triggers for LET, with cases of drug-induced LET following initiation of infliximab and LET in an HIV-positive man following immune reconstitution. It is well established, however, that LET exhibits photosensitivity in the majority of cases and can be reproduced with phototesting.9,11

The diagnosis of LET can only be confirmed with histologic analysis of the lesions by punch biopsy in conjunction with the clinical features. A perivascular and periadnexal lymphocytic infiltrate of T cells (CD4 > CD8) in the superficial and deep dermis with interstitial mucin deposition is frequently seen.9,11,13 In contrast to other types of CLE, the epidermis and dermal-epidermal junction show minimal or no change in LET.1,12 The majority of LET cases studied with direct immunofluorescence (DIF) showed a low prevalence of immunoglobulin or complement deposition at the dermal-epidermal junction, also differentiating it from other types of LE.9,12,13 In support of its categorization under CLE, LET is seen in patients with other forms of CLE simultaneously.1,10 Serologically, low-titer antinuclear antibodies may be detectable in a minority of cases.9,12

The differential diagnosis for LET includes Jessner lymphocytic infiltration of the skin (JLIS), granuloma annulare, erythematous plaques of acute LE, cutaneous mucinosis of systemic LE, DLE, pseudolymphoma, and polymorphous light eruption. JLIS bears many similarities to LET. It is an uncommon relapsing disorder with clinical and histologic findings often indistinguishable from LET, presenting with nonscaly red patches on the face, neck, and upper back. Slight differences in DIF between the two conditions have been recorded, but some investigators now regard them as variations of the same disease entity under CLE.9 Granuloma annulare exhibits histiocytes on histology, and DLE and systemic LE lesions have epidermal and dermal-epidermal junction involvement with necrotic keratinocytes. Mucin is absent in pseudolymphoma and polymorphous light eruption.9,11-13

Given the photosensitivity of LET, patients are encouraged to avoid sun exposure and utilize potent physical and chemical barriers from ultraviolet A and B light, such as creams with sun protection factor greater than 50 and photoresistant clothing. First-line therapies include topical corticosteroids and sun protection. Antimalarial agents, such as chloroquine (3.5-4.0 mg/kg/d) and hydroxychloroquine (6.0-6.5 mg/kg/d) have been shown to be effective as well. Methotrexate (7.5-10.0 mg/wk) and systemic corticosteroids (10-30 mg/d) are options in cases recalcitrant to topical therapies and antimalarial agents.9,12,14 The addition of topical tacrolimus 0.1% cream may lead to complete regression in patients with flares while on the antimalarial agents.14

The patient in the vignette was educated regarding effective sun protection. His lesions resolved completely after 1 week of treatment with oral hydroxychloroquine at 200 mg twice daily.

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Eman Bahrani, BA, is a medical student and Rana Mays, MD, is a dermatology resident at Baylor College of Medicine in Houston.


  1. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.
  2. Thornsberry LA, English JC 3rd. Etiology, diagnosis, and therapeutic management of granuloma annulare: an update. Am J Clin Dermatol. 2013;14(4):279-290.
  3. Maschio M, Marigliano M, Sabbion A, et al. A rare case of granuloma annulare in a 5-year-old child with type 1 diabetes and autoimmune thyroiditis. Am J Dermatopathol. 2013;35(3):385-387.
  4. Toro JR, Chu P, Yen TS, LeBoit PE. Granuloma annulare and human immunodeficiency virus infection. Arch Dermatol. 1999;135(11):1341-1346.
  5. Wu W, Robinson-Bostom L, Kokkotou E, et al. Dyslipidemia in granuloma annulare: a case-control study. Arch Dermatol. 2012;148(10):1131-1136.
  6. Li A, Hogan DJ, Sanusi ID, Smoller BR. Granuloma annulare and malignant neoplasms. Am J Dermatopathol. 2003;25(2):113-116.
  7. Güneş P, Göktay F, Mansur AT, et al. Collagen-elastic tissue changes and vascular involvement in granuloma annulare: a review of 35 cases. J Cutan Pathol. 2009;36(8):838-844.
  8. Mahmood T, Mansouri B, Menter A. Successful treatment of generalized granuloma annulare with adalimumab. Clin Exp Dermatol. 2015;40(5):537-539.
  9. Kuhn A, Bein D, Bonsmann G. The 100th anniversary of lupus erythematosus tumidus. Autoimmun Rev. 2009;8(6):441-448.
  10. Maize JC Jr, Costner M. Tumid lupus erythematosus: a form of lupus erythematosus. Arch Dermatol. 2010;146(4):451.
  11. Alexiades-Armenakas MR, Baldassano M, Bince B, et al. Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis. Arthritis Rheum. 2003;49(4):494-500.
  12. Hsu S, Hwang LY, Ruiz H. Tumid lupus erythematosus. Cutis. 2002;69:227-230.
  13. Rodriguez-Caruncho C, Bielsa I, Fernández-Figueras MT, et al. Lupus erythematosus tumidus: a clinical and histological study of 25 cases. Lupus. 2015;24(7):751-755.
  14. Verma P, Sharma S, Yadav P, et al. Tumid lupus erythematosus: an intriguing dermatopathological connotation treated successfully with topical tacrolimus and hydroxychloroquine combination. Indian J Dermatol. 2014;59(2):210. 
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