Sirolimus therapy for kaposiform hemangioendothelioma with long‐term follow‐up

Mammalian target of rapamycin inhibitors have shown promising results in the management of kaposiform hemangioendothelioma (KHE). The purpose of this study was to present our experience involving sirolimus therapy for KHE. A retrospective study was conducted to review the medical documents of 26 patients with KHE who were treated with sirolimus at our hospital between March 2012 and December 2016. Fifteen males and 11 females manifested KHE in infancy with an average age of 2.9 ± 1.8 months. Multiple anatomical sites were involved. Four patients had multifocal lesions, while 22 patients had solitary lesions. Twenty‐five patients had Kasabach–Merritt phenomenon (KMP). Twenty patients completed sirolimus therapy in 28.3 ± 12.5 months. Nineteen KHE lesions reduced to small residuals with platelet counts reaching normal levels 3.7 ± 2.8 weeks after treatment; one KHE lesion had no response to therapy. One patient with multifocal lesions died due to a severe infection, although the patient had previously responded to sirolimus. Five patients remained in treatment and had good responses with normal platelet counts. Nineteen patients with anemia had normal hemoglobin levels after 3.5 ± 1.9 weeks of treatment. Mild side effects were observed. The median follow‐up time was 32 months (26–60 months), with no evidence of recurrences. Sirolimus was shown to be efficacious in the management of KHE with an average course of 28 months. The time‐to‐response was variable, with an average of 1 week. After 4 weeks of treatment, the platelet count and hemoglobin level had normalized. Multifocal KHE with KMP is more severe than solitary KHE.     

Tumor‐stage mycosis fungoides in palmoplantar localization with large‐cell transformation and partial CD30 expression shows complete response to brentuximab vedotin

Mycosis fungoides in palmoplantar localization (MFPP) is a rare variant of MF that is confined to the hands and feet. Patients commonly receive treatment over many years for suspected palmoplantar dermatitis before the diagnosis is made. Most MFPP patients remain at patch or plaque stage, and often respond to treatment with radiotherapy. Herein, we describe a 77‐year‐old man who suffered 6 years of hand and foot dermatitis that failed multiple treatments, most notably TNF‐α inhibitors and mycophenolate mofetil. He eventually developed a tumor on the hand, which was biopsied to reveal a dense dermal infiltrate of large lymphocytes (CD3+/CD4‐/CD8‐/TCR‐BetaF1+/partial CD30+). A subsequent biopsy of an eczematous patch from his hand revealed an epidermotropic and syringotropic infiltrate comprised of smaller lymphocytes with a concordant immunophenotype and matching clonal peak with TCR gene rearrangement. He was diagnosed with MFPP and started on radiotherapy with a modest response; therefore, a decision was made to start brentuximab vedotin, which resulted in a complete response. MFPP is an exceedingly rare variant of MF that can show large‐cell transformation and progress in stage. We highlight a possible association between disease progression and immunosuppressants and the potential role for treatment with brentuximab.     

Evaluation of serum folate level before and after bath PUVA therapy in patients referred to Razi Hospital,Rasht, Iran

Ultraviolet (UV) radiation could disintegrate folate molecule, so phototherapy may reduce folate levels in the patients. The effect of phototherapy on serum folate in human body is questionable. We investigated the effect of bath PUVA therapy on serum folate level. This study was designed as a before–after study. Thirty‐two patients completed study during 2 years. Our variables were demographic data, folate levels before and 8 weeks after treatment and cumulative dosage of UVA during 8 weeks of treatment. Serum folate was evaluated with chemiluminescence immunoassay technique. All data were analyzed using SPSS 18 software. Folate level changes were statistically significant before and after bath PUVA therapy. There was no significant difference in folate levels in psoriasis patients compared with nonpsoriasis patients. In psoriasis patients, folate levels had no significant correlation with psoriasis activity index before treatment. Decrease in folate levels was more significant in fair‐skinned patients. There was no association between folate status and cumulative dosage of UVA. Bath PUVA therapy reduced serum folate level in our patients although none of them were folate deficient. Folate deficiency should be evaluated and corrected especially in fair‐skinned cases, as it may be aggravated by phototherapy.     

Management of long‐term therapy with biological drugs in psoriatic patients with latent tuberculosis infection in real life setting

Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long‐term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate‐to‐severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti‐TNF‐α and/or anti IL 12, 23 and/or anti‐CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X‐ray suggestive, without clinical, or microbiological evidence of active disease. All patients received prophylactic therapy for 9 months with isoniazid (INH) 300 mg/day, starting 3 weeks before the beginning of biological treatment. Fifty‐four patients completed prophylaxis with INH without any adverse events or intolerance; they continue the biological treatment without appearance of active tuberculosis. One patient developed tuberculosis pleurisy in course of treatment with etanercept. The infection has been treated and after a stable remission, treatment was restarted without tuberculosis reactivation. In this retrospective analysis, the prophylaxis of LTBI whit INH was effective and safe in longer follow‐up period.     

Efficacy of narrowband UVB vs. PUVA in patients with early‐stage mycosis fungoides

Introduction Mycosis fungoides (MF) is a non‐Hodgkin’s T‐cell lymphoma of the skin that often begins as limited patches and plaques with slow progression to systemic involvement. Narrowband ultraviolet (UV) B therapy has been proven to be an effective short‐term treatment modality for clearing patch‐stage MF. The effect of psoralen plus long‐wave ultraviolet A (PUVA) in the treatment of patch‐ and plaque‐type MF has also been thoroughly documented. Objectives The purpose of this study was to compare the efficacy and safety of narrowband UVB and PUVA in patients with early‐stage MF. Methods We analysed the response to treatment, relapse‐free survival and irradiation dose in 114 patients with histologically confirmed early‐stage MF (stage IA, IB and IIA). Results A total of 95 patients were treated with PUVA (83.3%) and 19 with narrowband UVB (16.7%). With PUVA, 59 patients (62.1%) had a complete response (CR), 24 (25.3%) had a partial response (PR) and 12 (12.6%) had a failed response. Narrowband UVB led to CR in 12 (68.4%) patients, PR in 5 (26.3%) patients and a failed response in 1 (5.3%) patient. There were no differences in terms of time to relapse between patients treated with PUVA and those treated with narrowband UVB (11.5 vs. 14.0 months respectively; P = 0.816). No major adverse reactions were attributed to the treatment. Conclusions Our results confirm that phototherapy is a safe, effective and well‐tolerated, first‐line therapy in patients with early‐stage cutaneous T‐cell lymphoma, with prolonged disease‐free remissions being achieved. It suggests that narrowband UVB is at least as effective as PUVA for treatment of early‐stage MF.     

Combined oral pulse and topical corticosteroid therapy for severe alopecia areata in children: a long‐term follow‐up study

There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated 65 children/adolescents with AA affecting >30% of scalp. Fourty‐three percent of patients had AA plurifocalis (AAP). Fifty‐seven percent had AA subtotalis (AAS), AAP+ophiasis (AAP+OPH), and alopecia totalis/universalis (AT/AU). Long‐term follow‐up (median 96 months) data were available for 69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks. Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion was applied 6 days a week. Hair growth was assessed on a scale ranging 0–100% of regrowth in individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth. 61.5% of all patients were considered good responders. Significantly, higher percentage of good responders was found in AA lasting ≤12 months. No patients had serious side effects. There was no change in stability of the hair status at the long‐term follow‐up. Most AA patients had beneficial effects with this protocol. Best results were in AAP and AAP+OPH. Combined topical and oral pulse corticosteroid therapy of AA in children shows long‐lasting results, without serious side effects.     

Therapeutic Hotline: Re‐induction may be useful to manage psoriasis relapse during long‐term maintenance treatment with infliximab: a retrospective analysis

Infliximab is an anti‐tumor necrosis factor‐alpha monoclonal antibody that is highly effective for the treatment of psoriatic disease. During maintenance treatment, some patients may experience a disease relapse, and, in such circumstances, dose intensification is frequently used to regain efficacy. We report our cumulative experience on the use of infliximab re‐induction in patients whose psoriasis relapsed during long‐term maintenance treatment with infliximab. From September 2005 to January 2009, 22 patients required re‐induction because of a relapse of their psoriasis. Re‐induction was effective in restoring response in most patients and was well tolerated in all cases, without occurrence of serious or unexpected adverse events.     

Treatment of epidermolysis bullosa acquisita with intravenous immunoglobulin in patients non‐responsive to conventional therapy: clinical outcome and post‐treatment long‐term follow‐up

Background Epidermolysis bullosa acquisita (EBA) is a chronic subepidermal blistering disease that is caused by antibodies binding to type VII collagen within anchoring fibrils. It is rare disease with an incidence of 0.25 cases per 1 000 000 population. Objective The objective of this study is to report the treatment outcomes with intravenous immunoglobulin (IVIg) therapy in 10 patients with severe and widespread EBA non‐responsive to conventional therapy. Methods Patients were treated according to a protocol published in a Consensus Statement to treat autoimmune mucocutaneous blistering diseases, including EBA with IVIg. A dose of 2 g/kg/cycle was used. Results Ten patients: four males and six females, all were North American Caucasian. The age at onset varied from 37 to 75 years (mean 57.4). A satisfactory clinical response was observed in all 10 patients. The patients received 16–31 cycles (mean 23.1) of IVIg over a period of 30–52 months (mean 38.8). Once IVIg was initiated, earlier drugs (prednisone, dapsone and others) were gradually withdrawn over a 5–9 month period (mean 7.2). Thereafter, IVIg was used as monotherapy. No serious side‐effects were observed. The follow‐up period since discontinuation of IVIg varied from 29 to 123 months (mean 53.9). During this follow‐up period, recurrence of disease was not observed. Conclusion The data suggest that IVIg can produce a long‐term sustained clinical remission in patients with EBA. In the patients, of this study concomitant therapy could be discontinued and IVIg was used as monotherapy.     

Predictive factors of response to pulse methylprednisolone therapy in patients with alopecia areata: A follow‐up study of 105 Japanese patients

Pulse corticosteroid therapy is effective for alopecia areata (AA) in the early stage. The risk and efficacy of this therapy for patients with several backgrounds, however, remains controversial. To explore the predictive factors of the response and risk factors of this therapy, data from 105 AA patients treated with methylprednisolone (500 mg) i.v. for 3 days consecutively in our facility were retrospectively analyzed. Among good responders, longer time from the onset to therapy was correlated with longer time required for hair regrowth (P = 0.037, n = 27). Multivariate models demonstrated that “severity”, “relapse” and longer “duration from the latest onset” were significantly and independently associated with poorer outcome (P < 0.01). “History of atopic dermatitis (AD)” was also associated with poorer outcome, but this correlation could be explained by the effect that duration from the latest onset of AA was longer among participants with AD. We propose that earlier initiation of pulse corticosteroid therapy is preferable for better outcome of AA, particularly among patients with AD. Clinicians should be mindful of the occurrence of mild adverse effects in the elderly patients.     

Serum galectin‐3 levels in patients with Behçet’s disease: association with disease activity over a long‐term follow‐up

Background There is a need for a laboratory marker that correlates with the clinical activity of Behçet’s disease (BD). Objective We aimed to investigate whether serum galectin‐3 (Gal‐3) levels were affected during the course of the disease with regard to disease activity. Methods A total of 131 subjects were involved in the study as follows: Group 1: BD active (n = 39); Group 2: BD inactive (n = 31); Group 3: Disease controls with leucocytoclastic vasculitis confirmed with a skin biopsy (n = 22); and Group 4: Healthy control subjects (n = 39). The BD patients were followed regularly and samples were taken in their active and inactive periods of the disease over a 2‐year period. Results Serum Gal‐3 levels were significantly higher in active BD patients (mean 2.38) than inactive BD patients (mean 0.63; P < 0.0001) and the healthy control subjects (mean 0.75; P < 0.0001). There was no significant difference between the leucocytoclastic vasculitis and active BD patients (P = 0.093). Serum Gal‐3 levels were positively correlated with clinical activity scores of active BD patients (r = 0.66, P < 0.0001). In addition, the Gal‐3 levels were significantly higher in the active disease period when compared with the inactive period during the follow‐up. There were no significant differences between the two inactive periods of the disease among the same patients. Further analyses revealed that patients with vascular involvement had significantly higher Gal‐3 levels than the other active BD patients (mean 7.57; P = 0.007). Limitations The limitation of the study is the small number of patients with vascular involvement in the active BD patient group. Conclusion Gal‐3 levels are correlated with the activity of Behçet’s disease especially with the vascular involvement.     

Excellent response to ustekinumab in a 9‐year‐old girl with severe psoriasis

We report the case of a 9‐year‐old girl with severe plaque psoriasis refractory to multiple topical and systemic therapies. Physical examination revealed extensive, erythematous plaques with overlying thick scales that covered more than 80% of her body surface area, which included the face, scalp, trunk, and limbs. Because of the severity of the disease and lack of treatment response to other systemic therapies, she was treated with ustekinumab. Three weeks after ustekinumab was initiated, her psoriatic lesions fully cleared.     

Long‐term follow‐up effect of omalizumab in chronic spontaneous urticaria and its association with serum C‐reactive protein levels

This study aims to determine the efficacy of omalizumab, a humanized monoclonal anti‐immunoglobulin E antibody, in patients with chronic spontaneous urticaria (CSU) refractory to conventional therapy, together with the evaluation of serum CRP levels. All the patients with a diagnosis of CSU who were continuously treated with omalizumab (300 mg/mo) for at least 3 months between June 2016 and July 2019 were included in this study. Urticaria activity score (UAS‐7) was used for assessment of disease activity. Serum CRP levels were also retrospectively analyzed. When UAS‐7 scores before the initiation of therapy were compared to the week 4, 12, 24, and 36 scores after the treatment, each were significantly different from the pretreatment results (P < .01). CRP level prior to treatment was found to be strongly correlated with baseline UAS scores of the patients' (P = .00). At the 12th week of treatment, decline of CRP level was positively and strongly correlated with the decline of UAS (P = .037). In this study, mean UAS decreased, mean rescue medication use declined, and overall therapeutic response improved with omalizumab treatment. Additionally, significant correlation between the decline of CRP levels and treatment response was found.     

Cost‐of‐illness in patients with moderate and severe chronic psoriasis vulgaris in Germany

Background: Data regarding costs of outpatient and office‐based care, as well as out‐of‐pocket expenses, for psoriasis patients in Germany are not available. Aim of this study was to assess average annual cost and cost per flare of outpatient and office‐based care for patients with moderate to severe chronic psoriasis vulgaris from several perspectives. Methods: In this multi‐center, cross‐sectional, retrospective and prospective cost‐of‐illness study, direct (medical and non‐medical) and indirect costs were considered from patient, third‐party payer (TPP) and societal perspectives. Results: Out of 227 patients enrolled consecutively in 17 centers, 192 cases could be analyzed. On average, TPP reimbursed 864 € per patient annually, 60 % for prescribed medication and 22 % for hospitalization. Patients spent 596 € yearly mainly for alternative therapies and OTC‐medication/skin care products as well as for additional expenses (e. g. ultraviolet lamp, clothes or cleaning agents). Indirect costs per patient amounted to 1,440 € yearly. Total annual costs per patient were 2,866 € and 4,985 € if treated with systemic drugs additionally. 1,173 € if treated topically and/or with phototherapy. Conclusions: The relatively high average annual costs per patient indicate need for efficient control of psoriasis. This cost‐of‐illness study provides basic data for further decision making, including economic assessment of innovative therapies for psoriasis.     

Epstein–Barr virus involvement in the pathogenesis of hydroa vacciniforme: an assessment of seven adult patients with long‐term follow‐up

Background Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein–Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T‐cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long‐term follow‐up. Objectives To assess EBV infection systematically in blood and in experimentally photoinduced lesions in adult patients with HV. Methods Repeated tests for EBV DNA blood load using real‐time polymerase chain reaction (PCR) and serological EBV tests were performed in seven adult patients with long‐term follow‐up. Skin samples from phototest‐induced lesions and surrounding normal skin were studied using PCR, in situ hybridization and electron microscopy. ZEBRA protein was detected using immunostaining. Thirty‐five patients with other photosensitive disorders were included as controls. Results The EBV DNA blood load was strongly positive in the seven patients with HV and negative in 34 of 35 of the patients with other photosensitive disorders (P < 0·001). The levels were higher in photosensitive patients with HV than in patients with HV in clinical remission. Ultrastructurally, viral particles were detected in lymphocytes and also in keratinocytes in three experimentally phototest‐induced lesions; they were not found in the surrounding normal skin. ZEBRA protein was also detected in phototest‐induced lesions, but not in the surrounding normal skin. Conclusion EBV is involved in HV pathogenesis and persists in adult patients with HV. A positive EBV DNA load, specific to HV in the spectrum of photosensitive disorders, might be a useful biomarker in HV.     

Long‐term effects of omalizumab on peripheral blood cells and C‐reactive protein levels in patients with chronic spontaneous urticaria

Omalizumab's mechanism of action is not well‐understood yet despite its strong therapeutic efficacy in chronic spontaneous urticaria (CSU). To determine the overall effect of omalizumab on peripheral blood cell counts and serum C‐reactive protein levels (sCRP) during a 1‐year follow‐up in patients with CSU. Data of 74 patients (male/female: 20/54) were reviewed from medical charts. Leucocyte counts, percentages of peripheral blood cells(lymphocyte, monocyte, neutrophil [PPBN], eosinophil, basophil [PPBB]) and sCRP were recorded at baseline, 3rd, 6th, 12th months of omalizumab treatment. Although a dramatic increase in the mean PPBB (±SD) was observed at the 3rd month, PPBB (%) gradually decreased after the 3rd month (PPBB: 0.38 ± 0.21 [baseline] vs. 0.59 ± 0.3 [3rd month], p = .002). However, 12th month PPBB remained higher than baseline (PPBB:0.38 ± 0.21 [baseline] vs. 0.46 ± 0.27 [12th month], p = .03). A dramatic decrease in the mean PPBN (%) was noticed within the first 3 months (PPBN:62.85 ± 8.97 [baseline] vs. 58.37 ± 9.07 [3rd month], p = .04), and 12th month PPBN remained lower than baseline values (PPBN: 62.85 ± 8.97 [baseline] vs. 60.31 ± 8.02 [12th month], p = .045).Mean sCRP (mg/dL) decreased rapidly within the first 3 months (sCRP: 1.09 ± 1.53 [baseline] vs. 0.56 ± 0.45 [3rd month], p = .17) and 12th month sCRP still remained lower than baseline levels (sCRP: 1.09 ± 1.53 [baseline] vs. 0.83 ± 1.06 [12th month], p = .01). Omalizumab substantially increases PPBB,and reduces PPBN accompanied by a reduction in sCRP especially in the first 3 months; however, these effects may continue in the long‐term. The alterations in peripheral blood cell ratios and sCRP may contribute to the therapeutic effect of omalizumab in CSU.     

Combination therapy with extracorporeal photopheresis,interferon‐α, PUVA and topical corticosteroids in the management of Sézary syndrome

Background: Extracorporeal photopheresis (ECP) is recommended for the treatment of Sézary syndrome (SS), the leukemic variant of cutaneous T‐cell lymphoma (CTCL). Several combination therapies are used to increase response rates to ECP. Patients and Methods: We report our experience with the combination therapy of ECP, interferon‐α, PUVA and topical corticosteroids in SS. Results: The treatment outcome in 12 SS patients was retrospectively analyzed and showed an overall response rate to this combination treatment of 42 % with 4/12 patients achieving a partial remission and 1/12 patients a stable disease. The median overall survival time was 42 months. We investigated several clinical and laboratory parameters as an indicator for a response to treatment in our patient cohort. A combined analysis of the erythroderma assessment scale, WBC, LDH, CD4/CD8 ratio and the number of Sézary cells revealed that a reduction of several parameters significantly correlated with response to treatment. The parameters which correlated best with response were number of Sézary cells, CD4/CD8 ratio and WBC. Conclusions: The investigated combination therapy was effective and well‐tolerated in a subgroup of SS patients but needs to be evaluated in a larger patient population.     

Keratoacanthoma centrifugum marginatum after photodynamic therapy with good response to oral retinoids and topical 5‐fluorouracil

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterized by progressive peripheral growth, and usually devoid of deep invasion. Different systemic (oral retinoids) or topical treatments have been reported, but there is not a well‐defined therapeutic protocol. We report the case of a KCM developing after photodynamic therapy (PDT) on the right leg of a 64‐year‐old woman. It was treated successfully with oral acitretin combined with topical 5‐Fluorouracil + salicylic acid for 5 months. This is the first case of KCM developing after PDT and successfully treated with oral retinoid combined with topical treatment.     

Anti‐tumor necrosis factor‐alpha therapy improves endothelial function and arterial stiffness in patients with moderate to severe psoriasis: A 6‐month prospective study

The aim of the present study was to determine if the use of the anti‐tumor necrosis factor (TNF)‐α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m² or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow‐mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty‐nine patients were studied. Anti‐TNF‐α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti‐TNF‐α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.