Included in the history and physical in a patient with suspected papuloerythroderma of Ofuji, the provider should elucidate the presence of pruritus, establish the status of atopy, and exclude all external triggering factors including infectious processes, malignancy, and drug-induced lesions. Minor criteria for the diagnosis of PEO include age over 55, male gender, eosinophilia, elevated IgE, and reduced lymphocyte count.[3] A full-body skin examination will likely reveal erythematous lesions comprised of flat, confluent, reddish-brown papules with distribution on the trunk, extremities, and extensor surfaces. In addition to these lesions, a positive deck-chair sign which is defined by exclusion of inframammary folds, axillary folds, inguinal creases, and popliteal fossae should be present.[11] Dermoscopy of PEO reveals multiple erythematous pin-point papules with surrounding whitish halos on an erythematous-pinkish background.[12]

Laboratory, histopathological, and clinical features are the hallmark of evaluation of papuloerythroderma of Ofuji. Laboratory tests including complete blood count, comprehensive metabolic panel, serum IgE, viral titers for Epstein-Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, and HIV, RPR, VDRL should be performed. Presence of lymphopenia elevated serum IgE, and peripheral eosinophilia are all consistent with the diagnosis of PEO. Histological evaluation of a punch biopsy should be performed in patients and reveals a perivascular infiltration of inflammatory cells including histiocytes, lymphocytes, and granulocytes. As a result of the similarity in clinical presentation of cutaneous T-cell lymphoma (CTCL) and that of PEO, patients should undergo flow cytometry and T-cell receptor clonality studies to rule out the possibility of misdiagnosis and to prevent further delay of treatment in patients with CTCL.[13]

Treatment of papuloerythroderma of Ofuji consists of initially finding the underlying etiology and treating the secondary disease; this may include the treatment of infectious processes or removal of pharmacological agents. Those with idiopathic disease currently have no gold standard of therapy; however previous cases have received treatment with photochemotherapy (PUVA - psoralen and ultraviolet A), oral steroid courses, and cyclosporine. A 9-month course of cyclosporine at 3mg/kg was noted to lead to complete resolution of skin-lesions with some residual post-inflammatory change.[9][10]

Differential diagnosis of papuloerythroderma of Ofuji should include the following: cutaneous T-cell lymphoma, secondary syphilis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Differentiation of cutaneous T-cell lymphoma and PEO is by flow cytometry and evaluation of clonal t-cell samples, secondary syphilis may be ruled out via VDRL and RPR testing, and DRESS can be differentiated via its acute presentation versus the more gradual, chronic course of PEO.[9]

The course of papuloerythroderma of Ofuji is generally indolent with remission occurring many years after the initial onset in idiopathic cases.[11] Those with secondary etiology leading to PEO may experience rapid clearance of lesions upon removal of the offending agents, or with the treatment of the underlying causes. In the absence of secondary bacterial super-infection, the overall disease progression is non-acute and consists of resolving pruritus which generally leads to complete resolution.

A significant complication of papuloerythroderma of Ofuji is secondary bacterial super-infection of the polygonal papular lesions likely due to excoriation. These secondary infections may lead to erysipelas or cellulitis and significantly impact patients overall well-being. These complications are manageable with brief oral courses of clindamycin or cefuroxime.[10] In addition to bacterial superinfection, delay of diagnosis of CTCL can also occur if there is a diagnosis of PEO without proper evaluation to rule out CTCL. Missing this critical diagnosis can lead to a deterioration of the clinical picture.

Patients suffering from papuloerythroderma of Ofuji should receive proper education on the correlations that exist between PEO and multiple internal malignancies, as well as its similarity and possible association with CTCL. Proper screening and evaluation to rule out these internal malignancies is a crucial component in the management of PEO and informing patients regarding the types of screening they should undergo will aid in adequate the evaluation of possible underlying disease processes.

Management of papuloerythroderma of Ofuji requires the participation of an interprofessional healthcare team approach. Besides the primary care provider, nurse practitioner and internist, the involvement of specialists in multiple fields to aid in the diagnosis of underlying malignancy should have participation at an early stage in the disease process. Pharmacists can be integral in helping determine when the condition is drug-induced as well as recommendations for pharmaceutical therapy, and nursing is often the primary point of contact for patients and families, providing education. [Level V] Patients with PEO should undergo evaluation via a gastroenterologist to perform upper endoscopy and colonoscopy to rule out gastric carcinoma and adenocarcinoma of the colon. In addition to proper gastroenterological work-up patients should be evaluated for any hematological abnormalities and referred to hematology/oncology specialists if any cell line abnormalities, flow-cytometry abnormalities, or clinical features of malignancy are present.[4][5][6][7]