A Case of Noonan Syndrome and Kyrle's Disease: Coincidence or Causality?

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus and no chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle's disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d) but with complete and long-lasting resolution of symptoms as well. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD being debated, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroid, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PDs (3). NS is a relatively common RASopathy, an heterogenous group of genetic disease characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes were identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it was hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of our patient's illness. Our patient suffered from diffuse keratosis pilaris, and one of the possible pathogenetic mechanisms of KD was theorized to be an abnormal epidermal keratinization with a secondary inflammatory dermic response (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, and is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Cicatricial alopecia associated with pemphigus.

Pemphigus is a chronic autoimmune bullous disease associated with the production of autoantibodies directed against desmosomal proteins, such as desmogleins 1 and 3. Here, we present the case of an 83-year-old woman who was referred to us with suspicious cicatricial alopecia of the scalp and a small, eroded lesion on the forehead, previously labeled as atrophic actinic keratosis after a skin biopsy. In our clinic, after a careful examination of the case, we decided to perform two new skin biopsies of the scalp on suspicion of an inflammatory disease.

A case of chronic granulomatous disease and acne: is isotretinoin a safe treatment?

We report the case of a patient with chronic granulomatous disease and acne treated with isotretinoin, who developed a diffuse staphylococcal skin infection during the therapy. Chronic granulomatous disease is a rare genetic disorder characterized by an altered innate immunity with an increased risk of potentially lethal bacterial and fungal infections. Although chronic granulomatous disease is rare, acne is a common manifestation in these patients, but there are no data about the gold standard therapy.

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

A Case of Noonan Syndrome and Kyrle Disease: Casualty or Causality?

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus or chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with a hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d), but with a complete and long-lasting resolution of symptoms. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD still being under debate, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules, with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroids, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PD (3). NS is a relatively common RASopathy, a heterogenous group of genetic diseases characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes have been identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair, are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it has been hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of the patient's illness. Our patient suffered from diffuse keratosis pilaris, and an abnormal epidermal keratinization with a secondary inflammatory dermic response is among the suggested possible pathogenetic mechanisms of KD (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, which is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Angiosarcoma and Vascular Surgery: A Case Report and Review of Literature.

INTRODUCTION: Angiosarcomas (AS) are rare and aggressive neoplasms originating from the endothelium: they represent less than 2% of all soft tissue sarcomas and usually have a poor prognosis. Although more often primary, different risk factors have been described and some cases are associated with vascular surgery. Materials and Methods: We present the case of an 84-year-old man who developed an AS on his thigh 3 years after a popliteal bypass with autologous saphenous vein. We performed a thorough review of the literature describing the main characteristics of the 25 cases (including ours) of AS associated with vascular surgery reported from 1981 to 2022. Results: Most of the patients were males (21 men vs 4 women) with a range age of 50-84 years. Most of AS are associated with Dacron grafts (12 cases), the overall mean time to onset is 7.8 years after surgery. The most common presenting symptoms are pain (20 cases) and weight loss (10 cases), while cutaneous presentation is uncommon; indeed, violaceous and painful papules, plaques, nodules, and skin ulceration have been found in 3 cases only. Due to unspecific symptoms, differential diagnosis is often difficult and a biopsy for histological confirmation is mandatory. Conclusion: Even if it seems to be a very rare complication, AS should always be considered in patients with compatible symptoms and who have undergone vascular surgery in the past.

Acral perineurioma: A case report of a rare neoplasm successfully treated with autologous skin graft reconstructive surgery.

Soft tissues perineurioma is a rare nerve sheath tumor that affects most of all the subcutaneous tissue. Even if it could present as a large mass, it is a benign neoplasm for which a complete surgical excision represents the gold standard treatment. Considering that it usually affects acral sites of young people, it can be challenging to perform a reconstructive surgery that allows a full functional recovery. We report the case of a woman in her 20s presenting a perineurioma of the sole of the right foot, a nodule of about 2 cm of diameter that compromised the support of the foot on the ground. We performed a radical surgical excision with no recurrence after 3 years of follow up and we obtained a full functional recovery thanks to an autologous full-thickness skin graft.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3. 75% Imiquimod

Abstract The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3.75% Imiquimod.

The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.

Diagnosis and management of cutaneous and anogenital lichen sclerosus: recommendations from the Italian Society of Dermatology (SIDeMaST).

Lichen sclerosus (LS) is a disabling chronic inflammatory disease of skin and genital mucous membrane causing itch, pain, dysuria and restriction of micturition, and significant sexual dysfunction and dyspareunia both in women and men. If left untreated, LS is associated with a high degree of sclerosis and scarring, as well as with an elevated risk of cancer in the genital area. Although a central role of autoimmunity is suggested, the pathogenesis of LS is still not clearly understood and the disease remains difficult to treat. The goals of treatment of LS are to alleviate symptoms and discomfort, prevent anatomical changes and prevent malignant transformation. This guideline has been developed by an Italian group of experts. It summarizes evidence-based and expert- based recommendations. The highest level of evidence favors the use of topical high potency corticosteroids; second- and third-line treatments include topical calcineurin inhibitors and topical retinoids, respectively. Surgical treatment has become the treatment of choice in male genital LS with persistent phimosis not responsive to medical treatment. The aim of this paper is to offer evidence-based and easily applicable recommendations for the management of LS.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Two-stage Ear Reconstruction with a Retroauricular Skin Flap after Excision of Trichilemmal Carcinoma.

Trichilemmal carcinoma is a rare cutaneous tumor with a frequently good prognosis but without standard criteria for surgical treatment. We aimed to show the results of a two-stage surgical approach that preserves the anatomical features of the ear. We report a case of 82-year-old man with trichilemmal carcinoma of the ear that was treated with a two-stage surgical approach. We observed that 5 months after the surgeries, the ear appeared entirely healed and there were no signs of recurrence; hence, our two-stage surgical approach allowed the anatomy of the ear to be preserved after the complete excision of the tumor.

Postherpetic neuralgia and recalcitrant cystic lesions following herpes zoster: A case report and review of treatment options.

Acute herpes zoster lesions in most cases are self-limited except in older and immunocompromised patients, wherein the pain can cause significant suffering. Postherpetic neuralgia is a painful situation for patients that can compromise the quality of life. Here, we report a 30-year-old healthy young man who developed treatment-resistant postherpetic neuralgia after herpes zoster (fourth/fifth thoracic segment) without any underlying immunocompromised state. He also developed some cystic lesions, which were removed by aspiration and surgery. The skin lesions improved 2 weeks after the surgery and postherpetic neuralgia was completely cured after 5 months, however cystic lesions recurred multiple times and were excised completely during each visit. Postherpetic neuralgia has a significant impact on the health-care cost borne by the society and affected individual, hence, it is essential to select appropriate treatment to manage the pain of postherpetic neuralgia.

Blue nevus of the nail: A case report and review.

Blue nevus (BN), in all its clinical variants, rarely affects the nail bed. This leads to difficulty in the diagnosis of BN within the nail bed as well as to challenges with regard to its treatment and follow-up management, not solely attributed to the intrinsic difficulty of the anatomical site. We present the first case in the literature of an acquired cellular BN entirely confined within the nail bed, in a female Caucasian patient. We propose diagnostic and therapeutic options based on personal clinical and surgical experience.