Dimitrios Alexandris

Introduction: Pembrolizumab is an immune checkpoint inhibitor widely administered for the treatment of various malignancies. Despite its effectiveness, its distinctive mechanism of action may lead to immune-related adverse events, most frequently affecting cutaneous tissues. Hair-related adverse events, although uncommon, include conditions such as alopecia areata and alterations in hair texture or type. Case report: A 63-year-old male patient presented with eyelash trichomegaly following two cycles of pembrolizumab infusion. Treatment and outcome: The patient experienced discomfort due to the eyelash trichomegaly, prompting him to consider discontinuing the treatment. However, the patient's neoplastic disease demonstrated a complete radiologic response, which encouraged him to continue the therapy. Discussion: This case illustrates a unique documentation of pembrolizumab-induced eyelash trichomegaly. While immune checkpoint inhibitors like pembrolizumab are known to cause hair-related adverse events, reports of eyelash trichomegaly remain rare. This case emphasizes the necessity for clinicians to remain vigilant about such uncommon side effects to ensure comprehensive patient management.

Background: Crusted scabies is a rare form of parasitic infection provoked by a massive infestation of the ectoparasite Sarcoptes scabiei varietas hominis on human skin. It is an extremely contagious type of disease and can even lead to a social stigma. In European countries like Greece, many cases remain undiagnosed for long periods, causing extreme distress in the patient’s everyday life and social environment. Case Description: Herein, we present a case of an 86-year-old woman with crusted scabies in Greece, who remained undiagnosed for 5 months. Massive hyperkeratotic plaques on the extremities, and face, palmoplantar keratoderma, and numerous small erythematous papules on the torso with extreme itch were the main clinical manifestations of the patient. Dermoscopy revealed the parasite. All necessary decontamination measures were taken by personnel. Treatment was administered and a complete cure of the disease was observed. Conclusions: In this case, the use of dermoscopy has attributed to precise crusted scabies diagnosis and acute pharmacological management of the patient. Early diagnosis of such diseases not only saves patients from lethal secondary infections, but also reduces the risk of a massive scabies outbreak. We also conducted a mini-review, analyzing all recent data concerning crusted scabies macroscopic, dermatoscopic, and histological images. All new information concerning the pathophysiological mechanism of crusted scabies manifestation, updated treatment options, and potential resistance to widely-used treatments are provided.

The use of micronutrients such as vitamin D could improve the response to viral vaccines, particularly in immunosuppressed and immunosenescent subjects. Here, we analysed the association between serum 25-hydroxyvitamin D (25OHD) levels and the immune response elicited by the BNT162b2 vaccine in a cohort of 101 healthcare workers naïve for SARS-CoV-2 infection. We observed no significant differences in anti-spike (S) IgG and T-cell responses according to the 25OHD status at baseline. However, significant correlations between the 25OHD concentration at baseline and (i) the anti-S response (p < 0.020) and (ii) the neutralizing antibody (NT) titre (p = 0.040) at six months after the second dose were detected. We concluded that adequate levels of vitamin D may improve the immune response to mRNA vaccines such as BNT162b2, and that further larger studies are warranted in order to confirm these preliminary observations.

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.

Introduction: Anti-EGFR targeted anti-cancer treatment is associated with various skin adverse events. Cetuximab is often associated with acneiform papules and skin disorders. Hypertrichosis cited in face pinnae and eyelash trichomegaly are seldom described. Case report: A 72-year-old female cancer patient presented deteriorating facial-pinnae hypertrichosis and eyelash prolongation post cetuximab infusion. Management and outcome: Consecutive cetuximab administration led to exaggerating hairy skin side effects, fully alleviated when the drug was discontinued. Discussion: To the best of our knowledge, this is the first reported case of an anti-EGFR-associated diffuse pinnae hypertrichosis presentation in a female patient in literature. This distinct entity can be easily diagnosed and manipulated with early drug withdrawal. An extensive review of relevant basic molecular research is provided to increase physicians’ awareness.

Introduction: Imatinib Mesylate (IM), a tyrosine kinase inhibitor, has been reported to cause several adverse reactions, most of them with cutaneous involvement. Non- Lichenoid IM associated skin reactions have been sufficiently- recorded. To our knowledge, Lichenoid Drug Eruption (LDE) is recorded in a minority of registries. Case report: To describe an LDE induced case by IM treatment. Treatment and outcome: Histological Confirmation and promptly dermatological consultation relieved successfully the cutaneous adverse event. Discussion: Ongoing expansion of IM usage in a wide spectrum of new indications is more likely to make physicians experience such LDE cutaneous side effects more often. Hence, they should be highly suspicious to early detect these distinct histologic entities, handle these undesired complications and guarantee satisfactory immediate outcomes, avoiding frivolous IM dosage modifications.

Introduction: New Immuno- Checkpoint inhibitors (ICIs) functioning as PD-1- PDL-1 blockers are nowadays used in a majority of anticancer treatments. Many immune- related Adverse Events (irAEs) are published daily; severe skin toxicities, Stevens Johnson/ Toxic Epidermal Necrolysis (SJS/TEN) are seldom reported. Case report: Herein, we present two interesting skin sever toxicity cases of lung cancer patients, undergoing PD-1- PDL-1 Immunotherapy. In both cases, a morbilliform rash with documented histological Toxic Epidermal Necrolysis Pattern /Stevens Johnson findings, was thoroughly studied. Management & Outcome: Both cases were therapeutically managed according to guidelines with different outcome. Discussion: Two focused cases of irAEs, is the rationale, to briefly review mechanisms of major toxicities caused by PD-1/PD-L1 blockade, and present all new data in their precise management. ICIs’ association with SJS/ TEN still remains unclear; underlying urgent need for further studies. It is important to alert physicians to promptly identify life threatening irAEs. Being familiar, provides management efficacy, safe resolve and encourage beneficial balanced cost effective treatments.