Treatment outcomes in patients with papuloerythroderma of Ofuji: A systematic review

To the Editor: Papuloerythroderma of Ofuji (PEO) is a rare disorder characterized by pruritic erythematous papules, which progress to fold-sparing erythroderma.1Teraki Y. Inoue Y. Skin-homing Th2/Th22 cells in papuloerythroderma of Ofuji.Dermatology. 2014; 228: 326-331Crossref PubMed Scopus (11) Google Scholar,2Torchia D. Miteva M. Hu S. Cohen C. Romanelli P. Papuloerythroderma 2009: two new cases and systematic review of the worldwide literature 25 years after its identification by Ofuji et al..Dermatology. 2010; 220: 311-320Crossref PubMed Scopus (41) Google Scholar Currently, there is no standardized therapeutic approach for PEO. The aim of this systematic review is to summarize treatments and outcomes for patients with PEO. This systematic review was registered on PROSPERO (CRD42020222951) and followed PRISMA guidelines. EMBASE and MEDLINE in OVID were searched on October 22, 2020. A total of 82 studies were included. These studies described 212 treatments for 135 patients (mean age: 72.0 years) with PEO. The mean duration of the disease course was 2.6 years, with a predilection for males (83%, n = 112/135) and Japanese ethnicity (11.9%, n = 16/135) (Table I). Of all reported PEO cases, 47.4% were of primary or idiopathic etiology (n = 64/135) and 52.6% were secondary (n = 71/135), most commonly due to cutaneous T-cell lymphoma (n = 35/71) or HIV (n = 5/71).Table ISummary of demographic information in patients with PEODemographicsPooled totalPrimary PEOSecondary PEOSex (n, %) Female22 (16.3%)11 (17.2%)11 (15.5%) Male112 (83.0%)52 (81.3%)60 (84.5%) NR1 (0.7%)1 (1.6%)0 (0.0%) Total (n)1356471Age (years) Mean age72.072.471.7 Age range30-9736-9730-89 NR000Ethnicity African Canadian1 (0.7%)0 (0.0%)1 (1.4%) Asian4 (3.0%)2 (3.1%)2 (2.8%) Caucasian9 (6.7%)5 (7.8%)4 (5.6%) Hispanic1 (0.7%)0 (0.0%)1 (1.4%) Indian1 (0.7%)0 (0.0%)1 (1.4%) Jamaican1 (0.7%)1 (1.6%)0 (0.0%) Japanese16 (11.9%)4 (6.3%)12 (16.9%) Korean2 (1.5%)1 (1.6%)1 (1.4%) Pakistani1 (0.7%)1 (1.6%)0 (0.0%) NR99 (73.3%)50 (78.1%)49 (69.0%)PEO duration (months) Mean number of months31.039.525.5 Months Range0.5-3000.5-3000.5-132 NR342410Comorbidities associated with PEO onset Cutaneous T-cell lymphoma35 (25.9%)035 (49.3%) HIV5 (3.7%)05 (7.0%) Furosemide drug reaction2 (1.5%)02 (2.8%) Peripheral T-cell lymphoma2 (1.5%)02 (2.8%) Hepatocellular carcinoma2 (1.5%)02 (2.8%) Gastric cancer2 (1.5%)02 (2.8%) Esophageal cancer2 (1.5%)02 (2.8%) Myelodysplastic syndrome2 (1.5%)02 (2.8%) Hepatitis C Virus1 (0.7%)01 (1.4%) Dermatitis herpetiformis1 (0.7%)01 (1.4%) Acute myeloid leukemia1 (0.7%)01 (1.4%) Bullous pemphigoid1 (0.7%)01 (1.4%) Hodgkin's lymphoma1 (0.7%)01 (1.4%) Malignant lymphocytic lymphoma1 (0.7%)01 (1.4%) T-cell prolymphocytic leukemia1 (0.7%)01 (1.4%) Capillary leak syndrome1 (0.7%)01 (1.4%) Chronic lymphatic leukemia1 (0.7%)01 (1.4%) Colon cancer1 (0.7%)01 (1.4%) Bladder cancer1 (0.7%)01 (1.4%) Pancreatic cancer1 (0.7%)01 (1.4%) Lung cancer1 (0.7%)01 (1.4%) Scabies1 (0.7%)01 (1.4%) Eczematide-like purpura1 (0.7%)01 (1.4%) Follicular mucinosis1 (0.7%)01 (1.4%) Monoclonal gammopathy of undetermined significance1 (0.7%)01 (1.4%) Strongyloidiasis1 (0.7%)01 (1.4%) Choledocholithiasis1 (0.7%)01 (1.4%)NR, Not reported; PEO, papuloerythroderma of Ofuji. Open table in a new tab NR, Not reported; PEO, papuloerythroderma of Ofuji. The reported treatments for primary and secondary PEO were the same aside from treatment differences addressing the underlying disease. Oral corticosteroids (13.7%, n = 29/212), psoralen and ultraviolet A (PUVA) (9.9%, n = 21/212), oral retinoids (3.8%, n = 8/212), and combination therapy were the most frequently reported treatments with favorable patient outcomes (Table II). Of the 29 treatments utilizing oral corticosteroids, 31.0% resulted in complete resolution (n = 9) within 24.0 days, 55.2% in partial resolution (n = 16) within 38.0 days, 10.3% in no resolution (n = 3), and 3.4% in worsening (n = 1). PUVA treatments resulted in complete resolution in 61.9% (n = 13/21) of cases within 105.0 days, partial resolution in 33.3% (n = 7/21) of cases within 106.5 days, and worsening in 4.8% (n = 1/21) of cases. Oral retinoid treatment led to complete resolution in 87.5% (n = 7/8) of cases within 25.0 days and partial resolution in 12.5% (n = 1/8).Table IISummary of treatment outcomes in patients with primary and secondary PEOPEO treatmentNumber of patients treated (n)Complete resolutionTime to complete resolution (days)Partial resolutionTime to partial resolution (days)No resolutionWorseningMean follow-up period post treatment (months)Monotherapy Corticosteroid (oral)299 (31.0%)24.0 (n = 2)16 (55.2%)38.0 (n = 3)3 (10.3%)1 (3.4%)70.7 (n = 14) PUVA2113 (61.9%)105.0 (n = 10)7 (33.3%)106.5 (n = 4)0 (0.0%)1 (4.8%)72.9 (n = 14) Corticosteroid (topical)91 (11.1%)14.0 (n = 1)5 (55.6%)NR3 (33.3%)0 (0.0%)3.0 (n = 1) UVB83 (37.5%)NR1 (12.5%)NR4 (50.0%)0 (0.0%)108.0 (n = 1) Retinoid (oral)87 (87.5%)25.0 (n = 7)1 (12.5%)NR0 (0.0%)0 (0.0%)24.0 (n = 1) Treating underlying condition72 (28.6%)2.0 (n = 1)5 (71.4%)14.0 (n = 1)0 (0.0%)0 (0.0%)13.0 (n = 2) Immunosuppressant63 (50%)120.0 (n = 1)2 (33.3%)NR1 (16.7%)0 (0.0%)10.5 (n = 2) IL-4 inhibitor31 (33.3%)98.0 (n = 1)2 (66.7%)90.0 (n = 1)0 (0.0%)0 (0.0%)8.3 (n = 3) Antihistamine20 (0.0%)N/A0 (0.0%)N/A1 (50.0%)1 (50.0%)108.0 (n = 1) Antibiotic21 (50.0%)90.0 (n = 1)1 (50.0%)NR0 (0.0%)0 (0.0%)NR Interferon-α11 (100.0%)28.0 (n = 1)0 (0.0%)N/A0 (0.0%)0 (0.0%)NR Antifungal10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)NR Androgen deprivation10 (0.0%)N/A1 (100.0%)28.0 (n = 1)0 (0.0%)0 (0.0%)NR No treatment11 (100.0%)NR0 (0.0%)N/A0 (0.0%)0 (0.0%)NRCombination therapy Corticosteroid (topical), antihistamine333 (9.1%)21.0 (n = 1)8 (24.2%)226.3 (n = 3)16 (48.5%)6 (18.2%)58.4 (n = 3) Corticosteroid (topical), corticosteroid (oral)90 (0.0%)N/A3 (33.3%)NR6 (66.7%)0 (0.0%)16.8 (n = 6) Corticosteroid (topical), PUVA94 (44.4%)NR3 (33.3%)7.0 (n = 1)1 (11.1%)1 (11.1%)108.0 (n = 6) Corticosteroid (topical), UVB72 (28.6%)NR5 (71.4%)NR0 (0.0%)0 (0.0%)87.6 (n = 5) Corticosteroid (topical), corticosteroid (oral), antihistamine53 (60.0%)10.0 (n = 3)2 (40.0%)NR0 (0.0%)0 (0.0%)20.0 (n = 3) Corticosteroid (topical), antihistamine, immunosuppressant∗Cyclosporine.,†Tacrolimus.20 (0.0%)N/A1 (50.0%)NR1 (50.0%)0 (0.0%)7.0 (n = 1) Corticosteroid (topical), antihistamine, PUVA20 (0.0%)N/A0 (0.0%)N/A1 (50.0%)1 (50.0%)8.0 (n = 2) Corticosteroid (topical), corticosteroid (oral), antihistamine, antibiotic‡Unreported type.20 (0.0%)N/A1 (50.0%)NR1 (50.0%)0 (0.0%)7.5 (n = 2) Corticosteroid (topical), antibiotic§Amoxycillin and clavulanic acid.10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)20.0 (n = 1) Corticosteroid (topical), antihistamine, UVB10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)12.0 (n = 1) Corticosteroid (topical), corticosteroid (oral), immunosuppressant‖Methotrexate.10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Corticosteroid (topical), corticosteroid (oral), antihistamine, UVB10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)12.0 (n = 1) Corticosteroid (topical), corticosteroid (oral), antihistamine, retinoid (oral), immunosuppressant∗Cyclosporine.10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)12.0 (n = 1) Corticosteroid (topical), PUVA, interferon-α10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)NR Corticosteroid (topical), retinoid (oral), interferon-α10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Corticosteroid (topical), retinoid (oral), PUVA11 (100.0%)90.0 (n = 1)0 (0.0%)N/A0 (0.0%)0 (0.0%)48.0 (n = 1) Corticosteroid (topical), retinoid (oral), UVB10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Corticosteroid (topical), UVB, interferon-α10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Corticosteroid (topical), antihistamine, antifungal10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)24.0 (n = 1) Corticosteroid (topical), antihistamine, immunosuppressant∗Cyclosporine., PUVA10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)10.0 (n = 1) Corticosteroid (topical), antihistamine, immunosuppressant∗Cyclosporine., UVB10 (0.0%)N/A1 (100.0%)NR0 (0.0%)0 (0.0%)NR Corticosteroid (oral), PUVA51 (20.0%)NR4 (80.0%)28.0 (n = 1)0 (0.0%)0 (0.0%)108.0 (n = 3) Corticosteroid (oral), immunosuppressant∗Cyclosporine.51 (20.0%)150.0 (n = 1)2 (40.0%)90.0 (n = 1)2 (40.0%)0 (0.0%)10.0 (n = 4) Corticosteroid (oral), antihistamine40 (0.0%)N/A2 (50.0%)30.0 (n = 1)2 (50.0%)0 (0.0%)2.0 (n = 1) Corticosteroid (oral), UVB20 (0.0%)N/A1 (50.0%)N/A1 (50.0%)0 (0.0%)NR Corticosteroid (oral), antihistamine, PUVA20 (0.0%)N/A2 (100.0%)NR0 (0.0%)0 (0.0%)NR Corticosteroid (oral), antihistamine, UVB10 (0.0%)N/A1 (100.0%)90.0 (n = 1)0 (0.0%)0 (0.0%)NR Corticosteroid (oral), PUVA, interferon-α10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Retinoid (oral), PUVA53 (60.0%)180.0 (n = 3)2 (40.0%)28.0 (n = 1)0 (0.0%)0 (0.0%)30.3 (n = 3) Retinoid (oral), UVB10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Retinoid (oral), PUVA, interferon-α11 (100.0%)365.0 (n = 1)0 (0.0%)N/A0 (0.0%)0 (0.0%)36.0 (n = 1) Retinoid (oral), antibiotic‡Unreported type., interferon-α10 (0.0%)N/A0 (0.0%)N/A1 (100.0%)0 (0.0%)NR Immunosuppressant, folic acid21 (50.0%)90.0 (n = 1)1 (50.0%)60.0 (n = 1)0 (0.0%)0 (0.0%)19.5 (n = 2) PUVA, antibiotic‡Unreported type.11 (100.0%)NR0 (0.0%)N/A0 (0.0%)0 (0.0%)NRn, number of eruptions, denominator for percentages; %, percentage.N/A, Not applicable; NR, not reported; PEO, papuloerythroderma of Ofuji; PUVA, psoralen and ultraviolet A; UVB, ultraviolet B.∗ Cyclosporine.† Tacrolimus.‡ Unreported type.§ Amoxycillin and clavulanic acid.‖ Methotrexate. Open table in a new tab n, number of eruptions, denominator for percentages; %, percentage. N/A, Not applicable; NR, not reported; PEO, papuloerythroderma of Ofuji; PUVA, psoralen and ultraviolet A; UVB, ultraviolet B. The most commonly used combination treatment was topical corticosteroids with oral antihistamines; however, it resulted in no resolution in 48.5% (n = 16/33) of cases, worsening in 18.2% (n = 6/33) of cases, partial resolution in 24.2% (n = 8/33) of cases, and complete resolution in 9.1% (n = 3/33) of cases. Of all combination therapies reported, the use of PUVA with either topical corticosteroids or oral retinoids resulted in the most number of complete resolution outcomes (44.4%, n = 4/9 and 60.0%, n = 3/5, respectively) and partial resolution outcomes (33.3%, n = 3/9 and 40.0%, n = 2/5, respectively). Our findings suggest that only a portion of patients with PEO respond well to treatment with oral corticosteroids, PUVA, oral retinoids, or a combination of PUVA with either topical corticosteroids or oral retinoids. One of the main challenges of treatment stems from the unknown pathogenesis of PEO, which is thought to be mediated by Th2 and Th22 cytokines.1Teraki Y. Inoue Y. Skin-homing Th2/Th22 cells in papuloerythroderma of Ofuji.Dermatology. 2014; 228: 326-331Crossref PubMed Scopus (11) Google Scholar Th2 cytokines are important mediators of IgE production and eosinophil survival,3Brandt E.B. Sivaprasad U. Th2 cytokines and atopic dermatitis.J Clin Cell Immunol. 2011; 2: 110Crossref PubMed Google Scholar which are both elevated in patients with PEO.2Torchia D. Miteva M. Hu S. Cohen C. Romanelli P. Papuloerythroderma 2009: two new cases and systematic review of the worldwide literature 25 years after its identification by Ofuji et al..Dermatology. 2010; 220: 311-320Crossref PubMed Scopus (41) Google Scholar Additionally, the percentage of IL-4, IL-13, and IL-22 producing CD4+ and CD8+ T cells were found to be increased in the circulatory systems of patients with PEO and decreased with disease remission.1Teraki Y. Inoue Y. Skin-homing Th2/Th22 cells in papuloerythroderma of Ofuji.Dermatology. 2014; 228: 326-331Crossref PubMed Scopus (11) Google Scholar Accordingly, the inhibition of IL-4 and IL-13 through the use of dupilumab was recently reported as a successful treatment for 2 patients with PEO.4Teraki Y. Taguchi R. Takamura S. Fukuda T. Use of dupilumab in the treatment of papuloerythroderma of Ofuji.JAMA Dermatol. 2019; https://doi.org/10.1001/jamadermatol.2019.0946Crossref PubMed Scopus (6) Google Scholar The limitations of our review include its small sample size and the observational nature of studies (9 case series and 73 case reports). Additionally, there were limited data available for treatment combinations, doses, timelines of resolution outcomes, and adverse events. Investigations are warranted to further explore other therapeutic modalities and to develop effective treatment guidelines for patients with PEO. Dr. Jensen Yeung has been a speaker, consultant, and investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, Leo, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant, and Xenon. Dr. Mufti, Dr. Lytvyn, Mr. Abduelmula Mr. Kim, and Ms. Sachdeva have nothing to declare.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.