The Great Mimickers of Rosacea

Topical Steroid–Induced Acne

Chronic use of topical corticosteroids on the face for several months can result in the appearance of monomorphic inflammatory papules (Figure 4). Corticosteroids can cause a dry scaly eruption with scattered follicular pustules around the mouth (perioral dermatitis).²³ This acneform eruption is indistinguishable from rosacea. However, the monomorphic inflammatory papules generally resolve within 1 to 2 months following discontinuation of the corticosteroid therapy.

^{Figure 4. Monomorphous small red papules on the cheek of a patient with steroid-induced acne. Photograph courtesy of Marc Silverstein, MD, Sacramento, California.}

Multiple pathways have been proposed as the mechanism for such reactions, including rebound vasodilation and proinflammatory cytokine release by chronic intermittent steroid exposure.²⁴ At first, the vasoconstrictive and anti-inflammatory effects of the steroids result in what seems to be clearance of the primary dermatitis for which the steroids were being used. Unfortunately, persistent use of steroids, particularly high-potency products, leads to epidermal atrophy, degeneration of dermal structures, and destruction of collagen, rendering the skin vulnerable to bacterial, viral, and fungal infections. In the end, the skin has the appearance of bright red rosacea with red scaly papules.

Rare Rosacealike Conditions

Carcinoid Syndrome

Carcinoid syndrome typically develops after hepatic metastasis from a carcinoid tumor when the circulating neuroendocrine mediators produced by the tumor can no longer be adequately cleared. Flushing is characteristic of carcinoid syndrome and usually presents on the face, neck, and upper trunk. Although rare, other types of cutaneous involvement also have been reported.²⁵ Bell et al²⁵ concluded that skin involvement is not uncommon in carcinoid syndrome, as all 25 patients with carcinoid syndrome showed cutaneous involvement in their case series. The investigators observed that chronic flushing eventually may become permanent and evolve into a rosacealike picture.²⁵

Cases of carcinoid syndrome that were misdiagnosed as rosacea have been reported in the literature.^26-28 Creamer et al²⁶ reported a case of a 67-year-old woman who initially was diagnosed with rosacea; it took 1 year to finally arrive at the correct diagnosis of multiple endocrine neoplasia type 1 after developing a malignant carcinoid tumor and a parathyroid tumor.

Cutaneous Lymphoma

B-cell neoplasms with skin involvement can present as primary cutaneous lymphomas or as secondary processes, including specific infiltrates of nodal or extranodal lymphoma or leukemia.²⁹ B-cell lymphomas involving the skin have a distinct clinical appearance, presenting as isolated, grouped, or multiple erythematous to violaceous papules, plaques, or nodules, usually in an asymmetric distribution (Figure 5). B-cell lymphoproliferative diseases simulating rosacea are extremely rare.²⁹ Nevertheless, B-cell lymphoma mimicking rhinophyma has been documented in the literature.^29-35

^{Figure 5. Small, erythematous, maculopapular lesions on the cheek and dorsal aspect of the nose in a patient with cutaneous B-cell lymphoma. Photograph courtesy of Marc Silverstein, MD, Sacramento, California.}

Barzilai et al²⁹ described 12 patients with B-cell lymphoproliferative neoplasms presenting with facial eruptions that clinically mimicked rosacea or rhinophyma. The clinical presentation included small papules on the nose, cheeks, and around the eyes mimicking granulomatous rosacea, and/or nodules on the nose, cheeks, chin, or forehead simulating phymatous rosacea. Three patients had preexisting erythematotelangiectatic rosacea and 1 had rhinophyma.²⁹

Lupus Miliaris Disseminatus Faciei

Lupus miliaris disseminatus faciei (LMDF) is an uncommon chronic inflammatory skin disorder characterized by the appearance of asymptomatic small, red to yellowish brown papules on the face.³⁶ This rare dermatologic disease usually is self-limited with spontaneous resolution of the lesions occurring within months or years; however, residual disfiguring scars may persist and usually are characteristic of LMDF.^36,37 The pathogenesis of LMDF is unclear, and controversy remains as to whether it is a distinct cutaneous entity or a variant of granulomatous rosacea.^38,39 It usually develops slowly as small, dome-shaped, red to yellowish brown papules in adults, most commonly appearing in men.³⁹ Lupus miliaris disseminatus faciei shares several common features with both acne vulgaris and rosacea. For example, the inflammatory lesions of LMDF are located on the central face and usually respond to treatments that typically are used to treat acne vulgaris and rosacea. However, LMDF can be distinguished histologically by more intense granulomatous inflammation and central caseation, occurring in the absence of an apparent infectious origin.³⁶

Tyrosinase Kinase Inhibitor Drug Eruptions

Sorafenib and sunitinib malate are multitargeted kinase inhibitors approved for the treatment of cancers such as renal cell carcinoma.⁴⁰ A study by Lee et al⁴⁰ reported that approximately 75% of patients treated with either sorafenib (n=109) or sunitinib (n=119) went on to develop at least one cutaneous reaction. Although hand-foot skin reaction was the most common and serious cutaneous side effect, other dermatologic manifestations, including alopecia, stomatitis, discoloration (hair or face), subungual splinter hemorrhages, facial swelling, facial erythema, and xerosis, were described. Facial changes such as swelling, yellowish discoloration, erythema, and acneform eruptions were described more frequently in patients treated with sunitinib than in those treated with sorafenib.⁴⁰

Other reports have described facial erythematous papules with sorafenib.⁴¹ In these patients, facial erythema usually occurs within 1 to 2 weeks after initiation of treatment, unlike hand-foot skin reaction, which usually develops later.⁴²

Epidermal Growth Factor Receptor Inhibitor Drug Eruptions

Monoclonal antibodies against the epidermal growth factor receptor (EGFR) (eg, cetuximab, panitumumab) and EGFR tyrosine kinase inhibitors (eg, gefitinib, erlotinib) are used in the treatment of several cancers. Use of these drugs has been associated with various dermatologic side effects, including rashes, paronychia and fissuring of the nail bed, hair changes, dry skin, hypersensitivity reactions, and mucositis.⁴³ The most frequent dermatologic side effect is a sterile follicular and pustular rash, often affecting the face, that is seen in more than half of the patients treated with these drugs.^43,44 These rosacealike facial lesions are accompanied by diffuse erythema and telangiectasia. In some cases, the pustules leave areas of erythema covered with greasy scaling, thus resembling seborrheic dermatitis.⁴³ In general, the pustular rash manifests within 1 to 3 weeks after the onset of treatment with EGFR inhibitors. The reaction typically resolves within 4 weeks of stopping treatment.⁴⁴ The etiology of the rash is unknown, but inhibition of EGFR may result in occlusion of hair follicles and their associated sebaceous glands, producing a rosacealike appearance.⁴⁵

Conclusion

Since its first medical description, rosacea has undergone extensive study regarding its pathogenesis and management. The most current investigations indicate microorganisms such as D folliculorum and H pylori as etiologic factors, though several other possibilities (eg, vascular abnormalities) have been suggested. Understanding the clinical variants and disease course of rosacea is important in differentiating this entity from other conditions that can mimic rosacea.

Acknowledgments—The authors thank Jennifer Rullan, MD, San Diego, California, and Jose Gonzalez-Chavez, MD, San Juan, Puerto Rico, for their assistance.