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.

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.

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.

Skin vascular lesions: A new therapeutic option with sequential laser-assisted technique.

Treatment of skin unaesthetic vascular lesions is still suboptimal. In this article, we present a multicenter study evaluating the efficacy and safety of the sequential 755 nm Alexandrite and 1064 nm ND:YAG lasers for the treatment of acquired and congenital vascular lesions of the skin. A total of 171 patients were included in the study (141 female and 30 male), median age 38, skin type from I to IV. Numbers of patients categorized for treated disease: 22 spider angiomas, 67 facial telangiectasia/spider veins, 58 leg telangiectasia/reticular leg veins, 24 port wine stains (PWS). Of those lesions 30.7% was on legs, 63.7% on face (6.7% on forehead, 10.1% on temples, 21.7% on cheeks, 25.2% on nose, 1.7% on chin) and 5.6% on chest. Spider angiomas required from 1 to 3 treatments. Facial telangiectasias had been treated from 1 to 4 times. Leg telangiectasias needed from 2 to 6 treatment sessions. Regarding PWS, it takes from 6 to 9 laser treatment to reach the clearance of the lesion. All the vascular disorders treated showed marked improvement while side effects were limited to low pain sensation and transitory fenomena. This sequential treatment is an effective, safe, and new approach for unaesthetic skin vascular lesions.

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.

Safety of the current drug treatments for vitiligo.

Introduction: Vitiligo is an acquired depigmenting skin disorder adversely affecting the patient's quality of life. Despite the presence of several treatment modalities, ranging from medical to physical to surgical options, none is curative. Each modality has its own drawbacks and side effects. Thus, the treatment modality needs to be tailored for each individual patient taking into consideration the disease characteristics and also its efficacy and safety to obtain a favorable risk-benefit ratio.Areas covered: This review highlights the different treatment modalities utilized in vitiligo up until 4 November 2019 along with their adverse effects and contraindications, if any.Expert opinion: All the medications have their own adverse effects and contraindications. We have included the most commonly used topical corticosteroids, which may result in striae, cutaneous atrophy, and tachyphylaxis, to the recently introduced biologics, which may induce hypersensitivity reactions, systemic toxicities, and even malignancies. However, more long-term studies are needed to assess the safety of these medications, especially the newer ones, to provide a safe and effective treatment for this disorder.

Biofibre® artificial hair implant: Retrospective study on 1,518 patients with alopecia and present role in hair surgery.

To treat alopecia, there are many surgical and nonsurgical treatments available nowadays. In the surgical one, the Biofibre® hair implantation system represents an important innovation with artificial hair with special physical, chemical, and mechanical features and the new Biofibre® Automatic device. Implant on 1,518 patients has been reported in this study where the Biofibre® hair implant technique is performed on men and women with varying degrees of baldness and for the treatment of various causes of alopecia such as androgenetic alopecia, burns, and scars. According to our experience, this technique gives immediate and visible results without scarring or hospitalization and the aesthetic results are very encouraging for both male and female patients with a rapid recovery of self-esteem and psychological well-being.

The Effectiveness of Local Surgical Technique in Treatment of Axillary Bromhidrosis.

BACKGROUND: Up to now, surgical excision of apocrine glands still has been a method that yields high treatment results and low rate of odour recurrent for patients, but many people worry about some serious complications that have been observed postoperatively, such as hematoma and skin necrosis. These prolong wound healing, leading to unsightly scars in the axillary fossae. AIM: We conducted this research to investigate the effects and complications of our surgical technique for axillary bromhidrosis. METHODS: Forty-three patients with axillary bromhidrosis were treated. An elliptical incision was made at a central portion of the area marked, with both tips of the ellipse along the axillary crease. The elliptical skin with the subcutaneous tissue was removed en lock. The adjacent skin was undermined to the periphery of the hair-bearing area with straight scissors. The undermined subcutaneous tissue was removed with curved scissors, and the skin was defatted to become a full-thickness skin flap. Any suspected hemorrhagic spots were immediately coagulated electrosurgically. Appropriate drains were placed, and the treated area was covered with thick gauze to each axilla. Arm movement was strictly controlled in the first 3 days post-operatively. RESULTS: Thirty-one patients have been followed up and evaluated for 6 months. 56 out of 62 axillae (90.3%) showed good to excellent results for malodor elimination. All patients reported a reduction in axillary sweating. There were two axillae of skin necrosis and three axillae of hematoma, with one patient receiving an anticoagulant from a cardiologist after the first day of surgery, to treat heart valve disease. The Dermatology Life Quality Index (DLQI) score decreased significantly, and the quality of life improved after the operation. CONCLUSION: Our technique is a simple surgical procedure and easy to perform helping to achieve results for high malodor elimination, with almost no serious complications. Patient's life quality improved significantly after the operation.

Anatomical Evaluation for Successful Dye Laser Treatment of Port Wine Stain in Vietnamese Patients.

AIM: To assess the efficacy in the treatment of port wine stain in the head and neck by using (Vbeam perfecta®). METHODS: Forty-two port wine stain patients were recruited at the National Hospital of Dermatology and Venereology, Hanoi, Vietnam. RESULTS: We reported an excellent response (43.8%) (76%-100% lightening), a good response (18.8%) (51%-75% lightening), fair improvement (18.8%) (26%-50% lightening), and no response (18.8%) (0%-25% lightening). CONCLUSION: In conclusion, pulsed dye laser is an excellent technique to remove port wine stains on the face and neck.

Efficacy of Surgical Excision for Nevus Sebaceous - Vietnamese Experience.

BACKGROUND: Nevus Sebaceous (NS) is hamartoma predominantly composed of sebaceous glands and is classified as a type of epidermal nevus. In most case, clinical manifestation of NS is typical, so histopathology examination is important only in atypical lesions for its risk of malignancy. Clinical symptoms are plaques or papules (100%), appearing in the head area (100%) with smooth surface (65.8%), usually with hair loss (60.7%). The histopathology is mostly characterized by the image of sebaceous gland hyperplasia (100%), no hair follicles (60.7%) or immature follicles (14.3%). AIM: The aim of our study is describing clinical and histopathological manifestation, make diagnosis and evaluate the best therapy. METHODS: Our study recruited 38 patients with NS, 3 patients (7.9%) with atypical aspects. All patients were treated by surgical excision. RESULTS: Complications as hair loss and infections were reported in 36.8% patients. No patients had recurrence after one year of treatment. CONCLUSION: Based upon our experience, surgery is cheap, simple, associated with high aesthetics effectiveness and low recurrence rate, proposing as the first choice for treatment of NS.

Serial Excision for the Treatment of Giant Congenital Melanocytic Nevus: The Vietnamese Way.

AIM: To investigate the efficacy of plastic surgery in the treatment of giant congenital melanocytic nevus (GCMN). METHODS: We enrolled 20 patients with 44 lesions and performed one of the following procedures: serial excision, skin grafting, tissue expansion, primary skin closure, distant flap, and adjacent flap. We assessed the outcome at 10 days and 6 months after surgery. RESULTS: Of 44 surgical sites, the most commonly used reconstruction surgeries were serial excision (16), skin grafting (16), and tissue expansion (6). Other types were rarely used. All patients with serial excision had good outcome. A total of 81% and 19% of the patients with skin grafting had good and fair outcome, respectively. Around 83% and 17% of the patients with tissue expansion had good and fair outcome. No cases had bad outcome. CONCLUSION: In conclusion plastic surgery is effective in the treatment of GCMN. There are different techniques but serial excision, skin grafts, and tissue expansion are most commonly used.