The interesting article by Spano et al.[1]. offers an understanding regarding the efficacy and safety of anti-PD1 in patients living with HIV and cancer in clinical practice. In this case report, we detail a case of a patient with melanoma and chronically infected with HIV who is successfully treated with anti-PD1 after ineffective treatment with BRAF-MEK inhibitors. In April 2015, a 69-year-old Caucasian patient with HIV was treated with efavirenz 600 mg, abacavir 600 mg, and lamivudine 300 mg. The patient has a baseline CD4+ count of 370 cells/μl and an undetectable HIV viral load. An excisional biopsy on the right back region resulted in nodular melanoma, 13 mm Breslow, no ulceration, positive for S100, Mart1, and HMB45. Subsequent wide local excision had a negative result; however, sentinel lymph node biopsy revealed one lymph node involved. No metastases were found in a successive full-body PET. In May 2017, a brain MRI showed a 3 cm parietal lesion and multiple bilateral pulmonary lesions. Computed tomography (CT) showed a single T9 vertebral lesion. Due to the presence of BRAF V600E mutation, dabrafenib--trametinib therapy was initiated. Between 2017 and 2018 ,routine brain MRI documented the progressive development of small encephalic lesions, which were treated successfully with Gamma Knife radiosurgery. The pulmonary and vertebral secondary lesions remained stable. Unfortunately, in January 2019, the patient developed a new unresectable cerebellar lesion. Due to the documented disease progression, dabrafenib-trametinib therapy was discontinued and nivolumab (240 mg/2w) was instituted. The subsequent brain MRI in July 2019, demonstrated a reduction in dimension and contrast-enhancement of all the lesions, especially those in the parahippocampal and anterior horn of the left lateral ventricle regions (Fig. 1). The HIV viral load remained undetectable and the CD4+ count was 420 cells/μl.Fig. 1: (a and b) Postcontrast T1-weighted axial and coronal brain magnetic resonance images performed in April 2019 at the start of the treatment with nivolumab showing multiple enhancing brain and cerebellar lesions with leptomeningeal involvement in the right frontoparietal and para-hippocampal regions (arrow), associated with involvement of the anterior horn of the left lateral ventricle. (c and d) Follow-up MRI of the same patient reveals marked decrease in size and contrast-enhancement of the metastatic lesions seen in the right parahippocampal region and in the anterior horn of the left lateral ventricle 3 months after nivolumab treatment (arrows).Treatment of cancer has been revolutionized by Immune Checkpoint Inhibitors (ICI). This kind of therapy is particularly effective in melanoma, because of its high immunogenicity. Antagonizing PD-1 or CTLA-4 proteins on the surface of T cells, tumor-induced T-cell anergy is prevented, leading to a greater antitumor response by the host immune system. However, patients with HIV infection have been excluded from clinical studies of immunotherapy, so there is a lack of clinical data on the efficacy and safety of ICI therapy in these patients. Cancer is the leading cause of death among non-AIDS-defining illnesses in patients with chronic HIV infection, particularly the most immunogenic ones, such as melanoma [2]. Furthermore, HIV patients experience shorter disease-free and overall survival than the immunocompetent ones [3]. Immunodeficiency associated with chronic HIV infection increases the risk of developing cancer and causes the worst prognosis by disabling patients from mounting an effective immune response against tumor cells. HIV infection leads to CD4+ T-cell anergy, amplifying the expression of different immune checkpoint molecules on their surface [4]. Our patient was treated with: efavirenz 600 mg, abacavir 600 mg, and lamivudine 300 mg. In particular, efavirenz is known to induce CYP3A4, whereas dabrafenib is metabolized by the same enzyme. Efavirenz may lower the levels of dabrafenib reducing its antitumor activity. This may explain the disease progression during dabrafenib--trametinib treatment in our case. The strict correlation between HIV and melanoma therapy is underlined by the efficacy of nelfinavir, a protease inhibitor, in the prevention of BRAF melanomas growth, in combination with either MEKi or BRAFi, and of NRAS mutant melanomas in combination with MEK5. Further studies are needed to assess the mechanisms, the efficacy and safety of targeted therapy in HIV patients. Instead, there is no evidence that immune checkpoint inhibitors interact with HAART supporting the good response in our patient. A point of interest is the improvement of our patient's CD4+ cell count. The protracted antigen exposures during HIV chronic infection leads to an overexpression of PD-1 in HIV-specific T cells with consequent cell functional exhaustion, lower proliferation, cytokine production, and cytotoxic abilities. In addition, HIV-specific CD8+ T cells express multiple inhibitory receptors like CD160+, 2B4, TIM-3, and LAG-3. Furthermore, viral load is related to PD-1 expression that is reduced in patients undergoing effective HAART. PD-1 pathway inhibition seems to restore exhausted CD8+ T cells activate B-cell-producing virus-specific antibody, enhancing antiviral immune response and viral control [6]. According to some authors, the activation of the T-cell reservoir could increase the autoimmune phenomena in HIV population [7] but recent reviews of the literature indicate there are no differences compared with HIV-uninfected population [2–8]. Further studies are needed to clarify this aspect. In conclusion, ICI therapy may be considered as a beneficial option for HIV-infected patients with advanced melanoma leading to an important antitumor response and preventing HIV-induced T-cell anergy. Prospective studies are needed to validate this evidence. Acknowledgements Conflicts of interest There are no conflicts of interest.
For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel represent, at the same time, barrier and connection between the inner and the outer sides of the body. The most important genetic correlations involve the chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in innate and adaptive immunity. The genetic background represents the substrate to the common immune processes involved in psoriasis and IBD. In the past, psoriasis and IBD were considered Th1-related disorders. Nowadays the role of new T cells populations has been highlighted. A key role is played by Th17 and T-regs cells as by the balance between these two cells types. New cytokines and T cells populations, as IL-17A, IL-22, and Th22 cells, could play an important pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support the hypothesis of a common pathogenesis.
The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injections for facial symmetry and functional restoration. Follow-up PET-CT scans showed no interference or artifacts attributable to HA injection, allowing for accurate imaging results. This case suggests that HA fillers administered in oncology patients may not universally pose challenges or disrupt PET-CT imaging interpretation. Due to the possible false positives induced by fillers, the inclusion of aesthetic treatments in patients’ anamnesis is a crucial step to accurately interpret PET-CT images. Although maintaining high level of caution in interpreting PET-CT results after filler injection is essential, our case emphasizes the safety of this procedure in oncology patients undergoing follow-up PET-CT scans.
To assess the influence of etanercept, an anti-tumour necrosis factor (TNF)-α agent, on autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors.Patients with psoriasis underwent 5-min electrocardiogram (ECG) recordings before and after 24 weeks of etanercept therapy. Linear heart rate variability (HRV) analysis was performed.The study recruited 19 patients. Frequency-domain analysis showed a significant decrease in oscillatory components attributable to sympathetic activity (LF%) and a significant decrease in low frequency/high frequency (LF/HF) ratio following etanercept therapy.Treatment with etanercept in patients with moderate-to-severe psoriasis could affect cardiovascular autonomic regulation, and subsequently reduce cardiovascular risk.
The outbreak of coronavirus disease-2019 (COVID-19) is a public health crisis of global proportion. In psoriatic patients treated with biologic agents, evidence is not yet available on susceptibility to infection with the novel SARS-CoV-2 coronavirus, and data about the perception of COVID-19 and its impact on these patients are lacking. The aim of this observational, spontaneous study was the evaluation of the impact of anti COVID-19 measures in "fragile population" such as patients with a chronic inflammatory disease. Thus, we evaluated the impact of perceived risk on quality of life of patients with moderate to severe psoriasis, in our outpatient clinic, and how their perceptions changed before and after the adoption of Covid-19 emergency measures following the Italian Ministerial Decree in March 9, 2020. Using a series of questions, our study surveyed adult patients with moderate to severe psoriasis receiving treatment with biologic agents (n = 591), before and after the adoption of COVID-19 emergency measures. Most patients (97%) had been sufficiently informed by healthcare staff about COVID-19 spread. A significant change was observed in social activity reduction before and after the adoption of the measures (18% vs. 90% of patients; P < 0.0001). Similarly, patients were more likely to suspend ongoing therapy after the measures were adopted than before (87% vs. 34% of patients; P < 0.0001). Following the measures, older patients were significantly more inclined to suspend therapy and reduce social activities than younger patients. Government COVID-19 emergency measures further curtailed already reduced social activities in psoriatic patients, and led to a greater inclination to suspend biologic therapy, more so in older patients, despite there being no evidence to support this suspension. These vulnerable patients may need support from clinicians in order to maintain treatment adherence.
Thyroid Eye Disease (TED), also known as Grave's Ophthalmopathy, is an autoimmune disorder characterized by inflammation of orbital and periorbital tissues, leading to ocular symptoms like proptosis, eyelid retraction with corneal exposure and diplopia. About 50% of Graves' disease patients develop TED, with increased risk in women, smokers, and those undergoing radioactive iodine therapy.1 TED usually emerges concurrently with hyperthyroidism, with an initial inflammatory phase lasting up to 2 years followed by a quiescent phase, during which symptoms may plateau or improve. While mild TED is usually self-limiting, moderate-to-severe cases often persist, with proptosis being the least likely to resolve. Treatment varies based on disease activity and severity, emphasizing achieving euthyroidism and smoking cessation. Mild cases may require symptomatic relief and selenium supplements, while moderate-to-severe active TED may necessitate glucocorticoids, orbital radiotherapy, or immunomodulatory agents. In stable phases, surgical interventions may restore function and aesthetics.2 Minimally invasive options such as Hyaluronic acid (HA) and Botulinum toxin type A (BTX-A) offer alternatives for ineligible or surgery-averse patients, providing fine-tuning postoperatively. We present a case of a 42-year-old woman who was referred to our dermatology ambulatory with a history of bilateral TED. The patient reported a diagnosis of Graves' disease at the age of 38, associated with significant ocular symptoms. She underwent antithyroid therapy for 18 months, experiencing an improvement, but the ophthalmic condition persisted. Upon clinical evaluation, the patient reported weight loss in the past few months, accompanied by tachycardia. Significant eyelid retraction and proptosis were observed with aesthetic and functional discomfort, indeed the patient reported dryness and irritation. We decided to start treatment utilizing Vycross® HA filler. All injections were performed bilaterally, and the procedure was repeated over three separate sessions, spaced 1 month apart, for a total treatment period of 2 months. The following injection sites and volumes were used: three needle injections of 0.1 mL each were administered into the zygomatic arch (malar region). An additional injection of 0.2 mL was placed into the mid-cheek area at the bone level. In the lower cheek, one needle injection of 0.5 mL was performed at the bone level, followed by two more injections of 0.5 mL each using a 22-gauge cannula (70 mm length) at the deep muscular facial plane (DMFP) and the suborbicularis oculi fat (SOOF) levels, respectively. Two injections of 0.5 mL each, using a 22-gauge cannula (70 mm length), were conducted at the subcutaneous level in the lower cheek region. Two subcutaneous needle injections of 0.7 mL and 0.3 mL were administered in the labiomental angle and chin apex areas, respectively. Finally, a 0.3 mL needle injection at the bone level of the right temple, and a 0.7 mL injection on the left temple were administered, followed by one needle injection of 0.2 mL in central and lateral infraorbital area and 0.1 mL in the medial infraorbital area. There were no reported adverse effects and the result was extremely pleasing and remained stable at the 6 and 12-month follow-up visit (Figures 1 and 2). Managing TED is challenging. Surgical options, such as orbital decompression, strabismus correction, and eyelid surgery carry risks and uncertain outcomes, especially in acute cases, as well as prolonged recovery.2 Recently, noninvasive technique like HA fillers and BTX-A are emerging. BTX-A injections can be associated with ptosis and ecchymosis, requiring careful administration and monitoring.3 Additionally, its effects have a relatively short duration, necessitating repeated administrations.4 In contrast, HA fillers addresses both aesthetic and functional challenges with minimal invasiveness and reversibility thanks to the possible use of hyaluronidase and adjustability through repeat treatments.5 Vycross® fillers provide durable volume and structural support for correcting proptosis and eyelid retraction, with reduced inflammation and side effects compared to other fillers, ensuring natural results and better tissue integration.6 The patient was in the stable phase of TED, which is ideal for interventions as inflammation had subsided. Specific injection sites were carefully chosen to restore facial symmetry and volume, particularly in the cheek and temple areas, commonly affected in TED patients. Precise targeting across various anatomical planes offered a more balanced correction compared to singular injections. A combination of cannulas and needles was chosen to reduce the risk of bruising and swelling and ensure even filler distribution. This technique is particularly important for TED patients, who may have sensitive and inflamed tissues. The treatment involved three sessions spaced a month apart to allow gradual improvement and manage complications, with carefully calculated volumes at each site to ensure balanced, natural results and avoid overcorrection. Our study underscores the efficacy and safety of nonsurgical approaches such as HA fillers, as a versatile alternative for patients ineligible or averse to surgical interventions. Aesthetic interventions must consider the disease's activity and timing, ensuring treatments are administered after the inflammation has subsided to prevent complications like granulomas or nodules. In this particular case, we employed Vycross® technology to demonstrate promising outcomes, stability and favorable results over a 12-month follow-up. However, to make definitive claims about the safety, effectiveness, and favorable outcomes of HA fillers in the treatment of TED, larger and more comprehensive studies need to be conducted. Future research with a larger sample size will be necessary to confirm these preliminary findings and to establish standardized treatment protocols. All authors were responsible for the concept and design of the study, collection and collation of data, analysis, and interpretation of data, write an article, reviewing this article, final reviewing this article and graphics performance. All authors declare that they have no conflicts of interest. This study was reviewed by local institutional review board (Ethics Committee of the Medical University Sapienza: Approval number US2345). Written consent is given by patient. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Psoriasis is a chronic immune-mediated disease that can be challenging to treat, especially in patients with severe disease or high body weight. Tildrakizumab is a monoclonal antibody which inhibits IL-23, approved for moderate-to-severe psoriasis with a standard 100 mg dose. A 200 mg dose may provide greater efficacy for patients over 90 kg or with high disease burden.
Citation: Proietti I, Tolino E, Bernardini N, Di Fraia M, Skroza N, Potenza C. Efficacy of Cemiplimab in a Patient Affected by Cutaneous Squamous Cell Carcinoma and Myelodysplastic Syndrome. Dermatol Pract Concept. 2023;13(3):e2023178. DOI: https://doi.org/10.5826/dpc.1303a178
Erythroplasia of Queyrat (EQ) is a rare disease involving the mucosal and transitional surfaces of the penis. Effective treatment is necessary to minimize progression to squamous cell carcinoma. The standard therapy for EQ, partial or radical penectomy, is invasive; photodynamic therapy (PDT) may be an effective, non-surgical tissue-sparing option. We report the case of a 67-year-old patient with long-standing EQ who was suc-cessfully treated with methyl aminolevulinate-PDT (MAL-PDT). A complete clinical response, confirmedby incisional biopsy, was achieved af-ter fivesessions of every-other-week treatment. The patient experienced moderate edema, erythema and pain within 5-7 days after the treatment, without urination problems. Our experience and a review of the published literature suggest that MAL-PDT may represent a valuable treatment option for selected cases of histopathologically-confirmed EQ.
