Herpes zoster in Belgium: a new solution to an old problem.

Herpes zoster (HZ) is caused by reactivation of the varicella-zoster virus. The life-time risk of developing HZ is ~ 30%. Management of HZ can be challenging due to limited efficacy of oral antivirals on pain control, and neuropathic pain that may require aggressive management. Post-herpetic neuralgia (PHN) can cause substantial pain and occurs in up to one-quarter of patients with HZ. Up to 48,000 HZ cases are estimated to occur annually in Belgium, estimated to cost almost 7 million euros in treatment. The recombinant zoster vaccine (RZV, Shingrix, GSK) was approved in Europe in 2017. In 2022, the Belgian Superior Health Council recommended vaccination with RZV for immunocompetent adults aged ≥ 60 years, and immunocompromised patients aged ≥ 16 years, including those receiving immunosuppressive therapy, in particular Janus kinase inhibitors. RZV showed high age-independent efficacy in preventing HZ infection and in clinical trials that has since been confirmed in real-world effectiveness studies. In clinical trials, protection was sustained for at least 10 years after vaccination. As of 1 November 2023, RZV is reimbursed for three immunocompromised patient groups aged ≥ 18 years: malignancy treated in the past 5 years, HIV infection, and organ or haematological stem cell transplantation or are a transplant candidate. HZ is vaccine-preventable and RZV provides a highly effective tool for HZ prevention. While reimbursement for some at-risk groups is welcomed, reimbursement currently falls well short of Superior Health Council recommendations. Adult immunisation strategies should be promoted to achieve high vaccination coverage against HZ, contributing to healthy aging in Belgium.

What is the context?Shingles (herpes zoster) is a common disease in adults that occurs more frequently as people age. The shingles' rash is frequently intensely painful. Antiviral treatments and pain killers can help, but they are usually not fully effective in reducing pain or shortening the disease.Shingles can be prevented in more than 90% of adults by vaccination.What is new?In 2022, the Belgian Superior Health Council recommended vaccination with recombinant zoster vaccine for immunocompetent adults aged ≥60 years, immunocompromised patients, including those receiving immunosuppressive therapy aged ≥16 years.What is the impact?Implementation of the new recommendations can be expected to lead to fewer cases of shingles and its most common complication ­ post-herpetic neuralgia. In turn, fewer patients will need prescriptions for antivirals, sedatives, and strong pain killers or other drugs with significant side effects.

Causes of Death in Cutaneous T-Cell Lymphoma Patients.

BACKGROUND: The advancing evolution toward a Th2 immune environment confers a progressive immunosuppression in patients with longstanding cutaneous T-cell lymphoma (CTCL). The conjunction of the disease-related immunosuppression as well as the immunosuppressive character of some CTCL treatments increase the risk of infectious and neoplastic diseases, sometimes with fatal outcomes. OBJECTIVES: The aim of the study was to prospectively study the causes of death in a cohort of CTCL patients, in a tertiary university skin cancer center. METHODS: All CTCL patients who died between 2008 and 2020 were included. The cause of the death was classified as directly or indirectly related or unrelated to CTCL. RESULTS: Over the study period, 31 (13F/18m) patients with CTCL died (mean age: 75.2 years), mean delay between diagnosis and death: 3.2 years (min: 1, max: 12 years), 58.1% of death causes were classified as indirect (infection), 12.9% directly related (blastic transformation), 22.5% unrelated, and 6.5% of unknown cause. 51.6% of mycosis fungoides (MF) patients who died had early-stage disease (1A-2A) or were on remission. 45.2% of dead patients had advanced-stage MF (2B-4B). Mean CRP level is increased in patients who died from infection whereas LDH level increased in patients with blastosis. A tertiary center is expected to manage of a higher proportion of CTCL patients with advanced-stage disease. CONCLUSIONS: As infection represented more than 50% of the causes of death in CTCL patients, particular attention should be given to preventive measures such as anti-infective vaccination. Regular surveillance of CRP and LDH levels could be helpful for follow-up of MF patients, respectively, with regards to infection and blastosis.

Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials.

BACKGROUND: Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144). OBJECTIVES: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials. METHODS: The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and ≥ 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125). RESULTS: A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and ≥ 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; ≥ 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; ≥ 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab. CONCLUSIONS: Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients. GOV IDENTIFIER: NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023.

Keratinocytes activated by IL-4/IL-13 express IL-2Rγ with consequences on epidermal barrier function.

Atopic dermatitis (AD) is a Th2-type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL-4 and IL-13. These cytokines activate type II IL-4Rα/IL-13Rα1 receptors in the keratinocyte. Whilst IL-2Rγ, that forms type I receptor for IL-4, is only expressed in haematopoietic cells, recent studies suggest its induction in keratinocytes, which questions about its role. We studied expression of IL-2Rγ in keratinocytes and its role in alteration of keratinocyte function and epidermal barrier. IL-2Rγ expression in keratinocytes was studied using both reconstructed human epidermis (RHE) exposed to IL-4/IL-13 and AD skin. IL-2Rγ induction by type II receptor has been analyzed using JAK inhibitors and RHE knockout (KO) for IL13RA1. IL-2Rγ function was investigated in RHE KO for IL2RG. In RHE, IL-4/IL-13 induce expression of IL-2Rγ at the mRNA and protein levels. Its mRNA expression is also visualized in keratinocytes of lesional AD skin. IL-2Rγ expression is low in RHE treated with JAK inhibitors and absent in RHE KO for IL13RA1. Exposure to IL-4/IL-13 alters epidermal barrier, but this alteration is absent in RHE KO for IL2RG. A more important induction of IL-13Rα2 is reported in RHE KO for IL2RG than in not edited RHE. These results demonstrate IL-2Rγ induction in keratinocytes through activation of type II receptor. IL-2Rγ is involved in the alteration of the epidermal barrier and in the regulation of IL-13Rα2 expression. Observation of IL-2Rγ expression by keratinocytes inside AD lesional skin suggests a role for this receptor subunit in the disease.

The Relevance of Skin Biopsies in General Internal Medicine: Facts and Myths.

INTRODUCTION: Non-dermatology medical specialties may refer patients for skin biopsies, searching for a particular diagnosis. However, the diagnostic impact of the skin biopsy is not clearly established. This article aims to assess the indications for, and evaluate the clinical relevance of, skin biopsies in non-dermatology medical specialties. METHODS: A questionnaire was sent to 23 non-dermatology specialty departments in a university medical center, requesting a list of indications for skin biopsies, as well as to 10 staff dermatologists to collect the indications of skin biopsies requested by non-dermatology specialties. Once the indications were collected, a literature search was performed to evaluate their clinical value and relevance. RESULTS: Eleven non-dermatology specialties provided a list of skin biopsy indications, to which staff dermatologists added seven more indications. A literature search revealed evidence-based medicine data for six diseases, that is, amyloidosis, peripheral autonomic neuropathy, Sneddon's syndrome, intravascular lymphoma, sarcoidosis, and chronic graft-versus-host disease. Results were questionable concerning infectious endocarditis, acute graft-versus-host-disease, and the lupus band test. Skin biopsy were not evidenced as useful for the diagnosis of calciphylaxis, systemic scleroderma, Behçet's disease, or hypermobile Ehlers-Danlos syndrome. For the diagnosis of Alport's syndrome, pseudoxanthoma elasticum, and vascular Ehlers-Danlos syndrome, skin biopsy is currently outperformed by genetic analyses. For diagnoses such as Henoch-Schönlein purpura and Sjögren's syndrome, skin biopsy represents an additional item among other diagnostic criteria. CONCLUSION: The usefulness of skin biopsy as requested by non-dermatology specialties is only evidenced for amyloidosis, peripheral autonomic neuropathy, Sneddon's syndrome, intravascular lymphoma, sarcoidosis, chronic graft-versus-host-disease, Henoch-Schönlein purpura, and Sjögren's syndrome.

Cemiplimab for locally advanced and metastatic basal cell carcinoma.

INTRODUCTION: Locally advanced basal cell carcinoma (laBCC) represents approximatively 1% of all BCCs. Metastatic BCC (mBCC) is even more rare. Most cases are observed in immunocompromised patients, particularly solid organ transplant recipients (OTRs). When surgery and/or radiation therapy for laBCC or mBCC is not reasonable, oral hedgehog inhibitor (HHI) therapy may be initiated. LaBCC or mBCC patients with primary or secondary resistance, progression or intolerance to HHIs could benefit from programmed cell death protein-1 (PD-1) inhibitors as this has recently been published for cemiplimab, a recombinant IgG4 human monoclonal antibody anti-PD-1 for the intravenous treatment of laBCC and mBCC. AREAS COVERED: Principal studies evaluating the efficacy and safety of cemiplimab for laBCC and mBCC are presented and discussed. EXPERT OPINION: Cemiplimab is the first FDA (2021) approved anti-PD-1 antagonist for the systemic treatment of laBCC and mBCC which had previously shown disease progression on or intolerance to HHIs. Experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is associated with a risk of organ graft rejection, advantages and disadvantages should be evaluated for every individual OTR patient with laBCC or mBCC, eligible for cemiplimab therapy.

Hereditary leiomyomatosis and acute lymphoblastic leukemia: A link through fumarate dyshydratase mutation?

BACKGROUND: : Hereditary leiomyomatosis (HL) is an autosomal dominant condition due to a variety of fumarate hydratase (FH) mutations in which individuals tend to develop cutaneous leiomyomas, multiple uterine leiomyomas and are at risk for developing aggressive papillary renal cell carcinoma. CASE PRESENTATION: : A 26-year-old man with a past history of acute lymphoblastic leukemia (T-ALL) presented with numerous painful light brown papules and nodules spread all over his body except for the head, appearing since infancy. Similar lesions were present in his mother's family. A cutaneous biopsy revealed a cutaneous leiomyoma. His mother died from metastatic uterine neoplasia and his sister suffered from leiomyoma of the uterus. No renal cancer was reported in his family. A heterozygous pathogenic variant was detected in the FH gene. CONCLUSION: : To our knowledge, this is the first case possibly linking HL and T-ALL through FH deficiency.

A Comprehensive Update of the Atypical, Rare and Mimicking Presentations of Mycosis Fungoides.

INTRODUCTION: Mycosis fungoides (MF) is the most frequent subtype of primary cutaneous T cell lymphomas (pCTCL). The diagnosis may be particularly difficult in the early stages as well as in atypical and rare clinical presentations. Furthermore, MF may simulate a large variety of common dermatologic disorders and patterns, both histopathologically and clinically. METHODS: A literature search was performed to provide a comprehensive update on the rare and atypical MF manifestations as well as the dermatoses and dermatological patterns that could be imitated by MF. RESULTS: A total of 114 publications were found describing a series of different dermatoses and dermatological patterns mimicked by MF, as well as some particular localizations of MF lesions and dermatoses that occur in preexisting MF lesions. CONCLUSIONS: The number of dermatoses that can be imitated by MF is ever-increasing. Patients with common dermatologic conditions that prove to be treatment refractory should be biopsied without delay, and sequentially as necessary, to prevent delay in diagnosis and progression of disease. Clinicopathologic correlation is the best way of diagnosis.

Necrobiosis Lipoidica following Breast Reduction.

Necrobiosis lipoidica (NL) is a rare granulomatous skin disorder of unknown physiopathology that is frequently associated with diabetes mellitus. The typical skin lesions of NL present as chronic, bilateral, well-defined red to yellow-brown plaques with telangectasias, a violaceous border and a waxy atrophic center. The lower legs are the most often involved areas, but NL may exceptionally develop on scar tissue following surgery. The treatment is very challenging and notoriously difficult. We report a 60-year-old diabetic woman who developed NL all along the surgical scars following breast reduction, without presenting NL on the lower legs. NL should be considered among the rare but possible skin healing complications of surgery.

Biologicals for moderate-to-severe plaque type psoriasis in pediatric patients.

INTRODUCTION: Psoriasis affects around 2% of children in Europe. The majority of cases is readily managed with topical treatments using corticosteroids without or with calcipotriol. More resistant and extensive moderate-to-severe cases require UVA or UVB phototherapies or conventional systemic treatment including ciclosporin, acitretin and methotrexate. However, these therapies are associated with a low tolerability and potential cumulative long-term adverse effects and toxicities. AREAS COVERED: About 15 years ago, the first biological appeared for the treatment of moderate-to-severe plaque type psoriasis in adult patients. Several years later, the first biologic treatment to be approved in children was etanercept, a soluble receptor that binds both tumor necrosis factor (TNF)-α and ß followed by adalimumab, a monoclonal antibody against TNF-α, and currently by ustekinumab, a monoclonal IL12/23 p40 antagonist and, very recently, secukinumab and ixekizumab, both IL17 antagonists. All these biologic treatments brought significantly improved treatment results compared to light-based therapies and conventional treatments and present very good tolerance and safety profiles. EXPERT OPINION: Due to their excellent efficacy and safety profiles ustekinumab, secukinumab and ixekizumab could currently be considered as a first-line treatment options for moderate-to-severe childhood and adolescent psoriasis requiring a systemic treatment.

Cemiplimab for locally advanced cutaneous squamous cell carcinoma: safety, efficacy, and position in therapy panel.

INTRODUCTION: Locally advanced cutaneous squamous cell carcinoma (lacSCC) is rare. Approximately one-fourth of the cases are observed among immunocompromised patients, in particular in solid organ transplant recipients (OTRs). LacSCC has a very poor prognosis. Surgery with or without radiotherapy remains the golden standard of treatment for cSCC. However, in advanced cases, there is a medical need for alternative treatment options. Classic systemic treatments include chemotherapy and/or EGFR inhibitors. Recently the effectiveness of programmed cell death protein-1 (PD-1) inhibitors has been demonstrated for lacSCC. Cemiplimab is a recombinant IgG4 human monoclonal antibody against the PD-1 protein for the intravenous treatment of lacSCC. AREAS COVERED: The principal studies evaluating the efficacy and safety of cemiplimab for lacSCC are presented. EXPERT OPINION: Cemiplimab is the first anti-PD-1 antibody that was FDA (2018) and EMA (2019) approved as a systemic treatment for lacSCC and/or metastatic cSCC when curative surgery or radiotherapy is no longer amenable. For this situation, experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is potentially associated with a risk of organ graft rejection, pros and cons should be evaluated for every individual OTR patient with lacSCC.

Value of Teledermoscopy in Primary Healthcare Centers: Preliminary Results of the TELESPOT Project in Belgium.

INTRODUCTION: Teledermoscopy using smartphone-based applications is becoming more and more important in a setting of increasing frequency of skin cancer and difficult access to specialized care. The TELESPOT project aimed to provide rapid diagnosis and speed up patient flow between primary healthcare centers and a tertiary care center in Belgium. The aim of the present study is to describe the development of an in-house smartphone-based dermoscopy application, evaluate its real-life value in a series of primary healthcare centers, and present preliminary diagnostic data. METHODS: Modified Likert scales were used to assess patient and general practitioner (GP) satisfaction rates for the system. Furthermore, a total of 105 photographic and dermoscopic images were acquired in a series of 80 patients at participating centers. RESULTS: Overall, patient and GP satisfaction levels were 89% and 94%, respectively. High-priority management was recommended in 7.6% of cases (8/105: 3 basal cell carcinoma, 1 primary cutaneous B-cell lymphoma, 1 Spitz melanocytic nevus, 1 congenital nevus, 1 in situ melanoma, and 1 invasive melanoma, proven by histology). CONCLUSIONS: The primary healthcare centers were highly satisfied with the TELESPOT project in terms of user-friendliness, efficacy, and reliability as well as in providing a reinforced image of first-line medicine efforts in combating skin cancer.

Cutaneous Breast Cancer Metastases Successfully Treated Using an Oxygen Flow Assisted Topical Administration of Methotrexate (OFAMTX).

INTRODUCTION: Cutaneous metastases of breast cancer remain a therapeutic challenge. Oxygen flow-assisted topical administration of methotrexate 5% (OFAMTX, 5% methotrexate in a carrier solution) has recently been proven to be an efficacious alternative treatment for extramammary Paget's disease, which is considered to be an in situ mammary adenocarcinoma of the epidermis. CASE REPORT: A 51-year-old patient with triple negative breast cancer presenting with biopsy-proven skin metastases on the chest agreed to a treatment with OFAMTX5%. The treatment duration was 2 weeks and consisted of twice-weekly sessions with OFAMTX5% applied to an area of skin of approximately 40 cm2. Skin biopsies were performed before and 2 months after procedure. The tolerance to the treatment was excellent, and no pain sensations were experienced. Two months post-procedure the treated area presented a post-inflammatory hyperpigmentation. No residual metastatic lesions were detectable on the control skin biopsy. Six months post-procedure the patient is still in clinical remission. DISCUSSION: OFAMTX5% represents an alternative skin-directed, painless, patient-friendly and efficacious adjuvant treatment for superficial metastatic lesions of breast cancer. Larger series are required to evaluate the potential of OFAMTX5% for the treatment of superficial metastatic lesions of breast cancer.

Risankizumab-Aggravated Crusted Scabies in a Patient with Down Syndrome.

Risankizumab, an interleukin (IL)-23 antagonist, is a highly effective treatment for moderate to severe psoriasis. Crusted scabies (CS) is a rare and severe form of scabies, occurring mainly in immunosuppressed patients and/or neurologically or mentally ill patients. A young girl with Down syndrome was diagnosed with a hyperkeratotic form of psoriasis. As treatment with topical dermocorticosteroids, UVB-phototherapy and acitretin for 6 weeks did not improve the lesions, two injections of risankizumab were administered. Following these injections, the lesions became rapidly even more severely crusted, and new lesions appeared on the extremities and the face of the patient. There was histological evidence of a high charge of scabies, leading to a diagnosis of CS. The patient was hospitalized and successfully treated by local permethrine and systemic ivermectine. This case suggests that even though anti-IL23 antagonists display an excellent overall safety profile, a particular caution for infections should still be respected in patients with underlying risk factors.

Granulomatous Reactions from Tattoos Following BRAF Inhibitor Therapy.

BRAF inhibitors may present several cutaneous adverse effects, including actinic keratosis, squamous cell carcinoma, keratoacanthoma, rashes, increased photosensitivity, panniculitis, palmoplantar and capillary involvement, pruritus and xerosis as well as granulomatous reactions. A 30-year-old patient with multiple tattoos received dabrafenib and trametinib for metastatic melanoma. After 4 months, he developed an induration and thickening strictly limited to several tattoos. Histopathology revealed nonnecrotizing granulomas in the dermis. Topical steroids relieved pruritus but not the granulomatous aspect of the tattoos. As far as we know, this is the first description of granulomatous reactions restricted to preexisting tattoos following BRAF inhibitor therapy.

Incidence of and Risk Factors for Cutaneous Scarring after Herpes Zoster.

BACKGROUND: About 20% of children have cutaneous scars following chickenpox. In contrast, skin scars are not often reported after herpes zoster (HZ). Risk factors for post-HZ scarring remain undetermined. OBJECTIVE: Our objective was to prospectively study the incidence of and risk factors for post-HZ scarring. METHODS: This was a 3-year prospective study of patients with HZ attending a tertiary university hospital. Baseline data, including age, sex, immunosuppression, prior history of scarring, severity and extension of HZ, afflicted HZ dermatome, and antiviral treatment received, were recorded. At 1 month after the HZ skin lesions had healed, patients were screened for skin scars at the prior HZ site. These patients were followed every 2 months for 6 months. RESULTS: At 6 months, 11 (9.7%) of 113 HZ patients still had post-HZ scarring (fair-skinned patients: hypopigmented [n = 3], hyperpigmented [n = 2], atrophic cicatricial [n = 3], and hypertrophic cicatricial [n = 1]; dark-skinned patients: severe hyperpigmented hypertrophic scarring [n = 2]). HZ was extensive and severe in all cases. Nine of the 11 patients were immunocompromised. Three cases had a history of hypertrophic/keloid scarring but no post-varicella scars. The most frequent location was the trunk (n = 5), followed by the cervical region (n = 3) and the face (n = 3). Given the study setting, it is possible that immunocompromized patients with severe HZ were overrepresented in this study. CONCLUSIONS: Scarring after HZ is probably overlooked. The principal risk factors seem to be severe HZ and immunosuppression. Hence, prompt instigation of antiviral treatment for HZ and HZ vaccination could help reduce the incidence of post-HZ scarring.