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1.
Indian J Dermatol ; 68(2): 170-177, 2023.
Article in English | MEDLINE | ID: mdl-37275806

ABSTRACT

Background: This study aims to investigate the anti-inflammatory effects of cinnamaldehyde in atopic dermatitis (AD) in the mouse model. Materials and Methods: Twenty-four mice were divided into four groups: Group A (control), group B [AD with no treatment (AD + NoTre)], group C [AD with corticosteroids (AD + Cort)] and group D [AD with cinnamaldehyde (AD + Cin)]. 2,4-dinitrofluorobenzene was used to form the AD model. Topical corticosteroid was applied to group C, and oral cinnamaldehyde was administered to group D. Dorsal skin biopsies were evaluated immunohistochemically with interleukin (IL)-25, IL-33, thymic stromal lymphopoietin and caspase-3. Results: Epithelial thicknesses were significantly higher in group B-D mice compared to group A (P = 0.002, 0.009, 0.004, respectively). Significantly, higher staining with IL-25 was observed in group B (AD + NoTre) and group D (AD + Cin) than in group A (control) (P = 0.003, 0.002, respectively). However, no significant difference was observed between group D (AD + Cin) and group B (AD + NoTre). All three groups (B-D) had significantly higher staining in terms of diffuseness of IL-33 compared to group A (control) (P = 0.002, 0.002, 0.002, respectively). Caspase-3 staining was significantly lower in group D (AD + Cin) than in group B (AD + NoTre) (P = 0.003, 0.002, respectively). Moreover, caspase-3 staining intensity was significantly lower in group D (AD + Cin) than in group C (AD + Cort) (P = 0.002). Conclusions: Our study demonstrated that IL-33, IL-25 and caspase-3 have a role in the pathogenesis of AD. Furthermore, cinnamaldehyde reduced caspase-3 activity more than topical corticosteroids and anti-inflammatory effects might be investigated in AD therapy with future studies.

2.
Int J Dermatol ; 62(2): 202-211, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36281828

ABSTRACT

BACKGROUND: A broad spectrum of skin diseases, including hair and nails, can be directly or indirectly triggered by COVID-19. It is aimed to examine the type and frequency of hair and nail disorders after COVID-19 infection. METHODS: This is a multicenter study conducted on consecutive 2171 post-COVID-19 patients. Patients who developed hair and nail disorders and did not develop hair and nail disorders were recruited as subject and control groups. The type and frequency of hair and nail disorders were examined. RESULTS: The rate of the previous admission in hospital due to COVID-19 was statistically significantly more common in patients who developed hair loss after getting infected with COVID-19 (P < 0.001). Telogen effluvium (85%) was the most common hair loss type followed by worsening of androgenetic alopecia (7%) after COVID-19 infection. The mean stress scores during and after getting infected with COVID-19 were 6.88 ± 2.77 and 3.64 ± 3.04, respectively, in the hair loss group and were 5.77 ± 3.18 and 2.81 ± 2.84, respectively, in the control group (P < 0.001, P < 0.001). The frequency of recurrent COVID-19 was statistically significantly higher in men with severe androgenetic alopecia (Grades 4-7 HNS) (P = 0.012; Odds ratio: 2.931 [1.222-7.027]). The most common nail disorders were leukonychia, onycholysis, Beau's lines, onychomadesis, and onychoschisis, respectively. The symptoms of COVID-19 were statistically significantly more common in patients having nail disorders after getting infected with COVID-19 when compared to the control group (P < 0.05). CONCLUSION: The development of both nail and hair disorders after COVID-19 seems to be related to a history of severe COVID-19.


Subject(s)
Alopecia Areata , COVID-19 , Nail Diseases , Nails, Malformed , Male , Humans , COVID-19/complications , COVID-19/epidemiology , Nail Diseases/epidemiology , Nail Diseases/etiology , Nail Diseases/diagnosis , Nails , Alopecia/epidemiology , Alopecia/etiology , Hair
3.
Acta Dermatovenerol Croat ; 31(3): 144-147, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38439724

ABSTRACT

Muir-Torre syndrome (MST) is a rare autosomal dominant subtype of hereditary non-polyposis colorectal carcinoma. The diagnosis is established based on the coexistence of sebaceous gland tumors and visceral organ malignancies. Mutations in the mismatch repair genes are responsible for Muir-Torre syndrome. Internal malignancies seen in MTS are most commonly colorectal, gastrointestinal system, endometrial, genitourinary system, breast, lung, brain, and hepatobiliary system malignancies. Detection of sebaceous neoplasia is essential in investigating Muir-Torre syndrome, allowing early detection of internal malignancies. Herein, we present the case of a patient with sebaceous adenomas, internal malignancies, and a new mutation detected during the genetic examination.


Subject(s)
Muir-Torre Syndrome , Humans , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , MutS Homolog 2 Protein/genetics , Mutation
4.
Indian J Dermatol ; 67(2): 205, 2022.
Article in English | MEDLINE | ID: mdl-36092209

ABSTRACT

Background: The etiopathogenesis and cold stimulation mechanism are not fully understood in cold urticaria (CU). Substance P (SP) is released from skin neurons as a result of cold stimulation. It causes mast cell degranulation and therefore causes mast cell chymase (MCC) release. Angiotensin-converting enzyme (ACE) plays a role in removing SP from the environment. ACE also catalyses the conversion of angiotensin I (AT1) to angiotensin II (AT2), like MCC. This study aims to investigate the role of SP, ACE and MCC in the pathogenesis of CU. Methods: Patients with acquired CU were included in the study. Two punch biopsies were taken from the urticaria plaque resulting from the stimulation and the intact skin without lesions. The samples were evaluated histopathologically. All samples were stained immunohistochemically with SP, ACE and MCC antibodies. Results: The number of patients included in the study was 21. In the plaque lesion, the presence of dermal neutrophil and eosinophil, neutrophil in the vascular lumen were found to be statistically significantly higher than intact tissue (p = 0.046, P = 0.014, P = 0.014). Strong positive staining was detected in the full thickness of the epidermis, vascular endothelial cells, eccrine and sebaceous glands with ACE. MCC was statistically significantly higher in lesional skin than lesion-free skin samples (p < 0.001). Conclusions: Mast cell maintains its central role in CU pathogenesis. SP, which causes neurogenic inflammation, may not be detected due to its rapid destruction in the tissue. Strong staining of ACE, which takes part in the local renin-angiotensin-aldosterone (RAS) system in the skin, should be documented quantitatively.

5.
Clin Rheumatol ; 41(9): 2875-2881, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35654917

ABSTRACT

Amiodarone can be used in a variety of arrhythmias. Given its widespread use, the probability of clinicians encountering its cutaneous adverse effects is high. A few cases of amiodarone-induced cutaneous vasculitis were reported in the literature, probably because it is underdiagnosed in clinical practice. Indeed, amiodarone-related cutaneous reactions may present a wide range of manifestations and are sometimes difficult to diagnose. Herein, we report a case with a sizeable necrotic ulcer on the left lower leg shortly after amiodarone exposure. A rigorous diagnostic study was performed before concluding the diagnosis of amiodarone-induced cutaneous vasculitis, which showed the histopathological features of leukocytoclastic vasculitis. The lesion was almost completely healed by the third month of discontinuation of amiodarone. We did a literature search and found seven cases which were reported as leukocytoclastic or lymphocytic vasculitis. We reviewed previous cases and presented our case in comparison to prior cases.


Subject(s)
Amiodarone , Vasculitis, Leukocytoclastic, Cutaneous , Amiodarone/adverse effects , Arrhythmias, Cardiac , Humans , Leg/pathology , Skin/pathology , Vasculitis, Leukocytoclastic, Cutaneous/chemically induced , Vasculitis, Leukocytoclastic, Cutaneous/diagnosis , Vasculitis, Leukocytoclastic, Cutaneous/pathology
6.
Ital J Dermatol Venerol ; 157(1): 47-54, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35176842

ABSTRACT

BACKGROUND: A wide variety of effects of irisin, as a myokine and adipokine, have been reported. Although there are some clues about its role in the modulation of immune response in the pathogenesis of immune-mediated diseases such as psoriasis, it has not yet been clearly elucidated. The aim of the present study is to investigate the relationship of irisin levels with inflammation and insulin resistance in patients with psoriasis. METHODS: This study was conducted in patients with moderate-to-severe psoriasis and healthy subjects who were admitted to Haseki Training and Research Hospital. In addition to routine laboratory analyses, hs-CRP, insulin, irisin, adiponectin, and leptin levels were measured. The association between irisin levels and study variables was assessed using univariate and multivariate analyses. RESULTS: A total of 42 non-diabetic patients with moderate-to-severe psoriasis and 43 healthy subjects were enrolled. The mean irisin, waist circumference, insulin, insulin resistance, and hs-CRP, and frequency of metabolic syndrome were significantly higher in psoriasis patients than healthy controls. Psoriasis and control groups were similar in terms of adiponectin, leptin, and Body Mass Index levels. Also, hs-CRP levels were positively and strongly correlated with irisin, adiponectin, and leptin levels. The median irisin level was 2.15 µg/mL. In the binary logistic regression analysis, CRP level (OR=1.14, 95% CI 1.005-1.29, P=0.042) and a BMI>30 kg/m2 (OR=5.9, 95% CI 1.02-34.4, P=0.048) were independent predictors of a higher irisin level. CONCLUSIONS: This study demonstrates that serum irisin levels are higher in patients with moderate-to-severe psoriasis than in healthy subjects. Irisin seems to be associated with inflammation, as measured by hs-CRP. More comprehensive studies are needed to clarify the effect of irisin, on immune-modulate response in patients with psoriasis.


Subject(s)
Insulin Resistance , Psoriasis , Body Mass Index , Fibronectins , Humans , Inflammation , Insulin Resistance/physiology
7.
São Paulo med. j ; 139(2): 186-189, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1181004

ABSTRACT

ABSTRACT CONTEXT: Various skin manifestations have been reported in coronavirus disease. It may be difficult to determine the etiology of these lesions in view of the increased frequency of handwashing during the pandemic, along with occurrences of irritant contact dermatitis and allergic contact dermatitis due to disinfectant use; usage of herbal medicine and supplements to strengthen the immune system; and urticarial or maculopapular drug eruptions due to COVID-19 treatment. The variety of associated skin manifestations seen with COVID-19 makes it challenging to identify virus-specific skin manifestations. Petechiae, purpura, acrocyanosis and necrotic and non-necrotic purpura, which can be considered as manifestations of vascular involvement on the skin, have been reported. CASE REPORT: Here, we report a case of eruptive cherry angiomas, which was thought to have developed due to COVID-19, with a papulovesicular rash on distal extremities that progressed over time to reticular purpura. CONCLUSION: The case presented had a papulovesicular rash at the onset, which evolved to retiform purpura, and eruptive cherry angiomas were observed. It should be kept in mind that dermatological signs may vary in patients with COVID-19.


Subject(s)
Humans , Male , Female , Middle Aged , Purpura/virology , Skin/virology , Skin Diseases, Viral/virology , Exanthema/virology , COVID-19/complications , COVID-19/virology , Hemangioma/virology , Skin/drug effects , Skin/pathology , Treatment Outcome , Skin Diseases, Viral/diagnosis , Skin Diseases, Viral/therapy , COVID-19 Testing , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/therapy
8.
Dermatol Ther ; 34(3): e14950, 2021 05.
Article in English | MEDLINE | ID: mdl-33724616

ABSTRACT

Coronavirus disease-2019 (COVID-19), which emerged in late 2019 and caused a pandemic, has significantly affected outpatient admissions to dermatology outpatient clinics. There have been changes in the number and composition of the patients who applied to the outpatient clinics. The dermatology outpatient clinic applications have dramatically decreased due to restrictions and prohibitions, and active participation of dermatologists in the field immediately after the pandemic. The composition of the diagnoses has also altered for reasons such as excessive use of hygiene products and types of protective equipment usage related to COVID-19. Intensive precautions have been taken in the first 3 months of the pandemic (March, April, and May). As of 12 May, controlled socialization started with new regulations. This period has been called "the normalization process." This study aims to evaluate the changes of the patients admitted to dermatology outpatient clinics within the normalization process. Despite the increasing number of COVID-19 patients and related deaths in the whole country with the new normal, the admissions to dermatology outpatient clinics have increased. During this period, acne and related diseases, pigmentation disorders, and viral skin infections had increased; dermatoses, xerosis cutis, and superficial fungal infections had reduced. It seems that nonurgent dermatological complaints affect the quality of life of patients and cause the need for an application. Although restrictions reduce these numbers, measures should be taken to protect patients and society during the ongoing pandemic.


Subject(s)
COVID-19 , Dermatology , Ambulatory Care Facilities , Disease Outbreaks , Humans , Quality of Life , SARS-CoV-2
9.
Sao Paulo Med J ; 139(2): 186-189, 2021.
Article in English | MEDLINE | ID: mdl-33566880

ABSTRACT

CONTEXT: Various skin manifestations have been reported in coronavirus disease. It may be difficult to determine the etiology of these lesions in view of the increased frequency of handwashing during the pandemic, along with occurrences of irritant contact dermatitis and allergic contact dermatitis due to disinfectant use; usage of herbal medicine and supplements to strengthen the immune system; and urticarial or maculopapular drug eruptions due to COVID-19 treatment. The variety of associated skin manifestations seen with COVID-19 makes it challenging to identify virus-specific skin manifestations. Petechiae, purpura, acrocyanosis and necrotic and non-necrotic purpura, which can be considered as manifestations of vascular involvement on the skin, have been reported. CASE REPORT: Here, we report a case of eruptive cherry angiomas, which was thought to have developed due to COVID-19, with a papulovesicular rash on distal extremities that progressed over time to reticular purpura. CONCLUSION: The case presented had a papulovesicular rash at the onset, which evolved to retiform purpura, and eruptive cherry angiomas were observed. It should be kept in mind that dermatological signs may vary in patients with COVID-19.


Subject(s)
COVID-19/complications , COVID-19/virology , Exanthema/virology , Hemangioma/virology , Purpura/virology , Skin Diseases, Viral/virology , Skin/virology , COVID-19/therapy , COVID-19 Testing , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Skin/drug effects , Skin/pathology , Skin Diseases, Viral/diagnosis , Skin Diseases, Viral/therapy , Treatment Outcome , COVID-19 Drug Treatment
10.
J Cutan Pathol ; 48(5): 611-616, 2021 May.
Article in English | MEDLINE | ID: mdl-33368594

ABSTRACT

BACKGROUND: Pigmented purpuric dermatoses (PPD) can clinically mimic many diseases. Histopathology provides a definitive diagnosis. The aim of the study is to reveal the features of patients with PPD and to determine the disease frequency in the differential diagnosis, especially mycosis fungoides (MF). METHODS: We retrospectively reviewed records of patients with PPD admitted to our hospital from January 2010 to May 2019. We studied the histopathological features of 127 patients, and performed pattern analysis on cases with a confirmed histopathologic diagnosis of PPD. Among the cases presenting with clinical features of PPD, but displaying different histopathological diagnoses, we focused on MF and tried to clarify the features of PPD-like MF. RESULTS: Overall, 389 patients were admitted to our hospital with PPD symptoms. Of them, 262 patients were diagnosed clinically and a histopathological examination was performed in 127 patients. Of 127, 87 were diagnosed with PPD, and in the remaining 40, non-specific features (9.4%), vasculitis (6.2%), pityriasis rosea (4.7%), MF (3.9%), suspected-MF (1.5%), and other dermatoses (%5.5) were detected. The biopsy findings of two patients showed PPD, but during follow-up, the diagnosis of MF was established. CONCLUSIONS: MF should be included in the differential diagnosis of PPD cases presenting with longstanding and widespread involvement.


Subject(s)
Mycosis Fungoides/pathology , Pigmentation Disorders/pathology , Pityriasis Rosea/pathology , Purpura/pathology , Vasculitis/pathology , Adult , Aged , Awareness , Biopsy , Child , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Mycosis Fungoides/diagnosis , Mycosis Fungoides/epidemiology , Pigmentation Disorders/diagnosis , Pityriasis Rosea/diagnosis , Pityriasis Rosea/epidemiology , Purpura/diagnosis , Retrospective Studies , Skin Neoplasms/pathology , Tertiary Care Centers , Vasculitis/diagnosis , Vasculitis/epidemiology
12.
Cutan Ocul Toxicol ; 39(4): 380-384, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33028137

ABSTRACT

INTRODUCTION: Epidermal growth factor receptor inhibitors (EGFRs) are chemotherapeutic agents used in multiple solid organ malignity. These medications have common dermatological side effects, particularly papulopustular (PPL) lesions. The management of the diagnosis and treatment processes for such side effects may facilitate the continuation of chemotherapy and enhance the patient's quality of life. OBJECTIVE: The objective of this study is to report the cutaneous side effects of EGFR inhibitors and to share treatment methods for such side effects. MATERIALS AND METHODS: In this prospective study, 59 patients using EGFR due to breast and colorectal carcinoma at the oncology unit of Haseki Training and Research Hospital were assessed. The patients for whom EGFR was initiated were examined at the beginning of the treatment at weeks 1 and 2, their demographic characteristics were recorded, and the patients who developed a skin rash were followed up from the onset of the lesion. The PPL side effects that developed in the patients and other dermatological findings were recorded. The PPL side effects were graded, and the treatment plans were reported. The study was conducted between February 2016 and February 2018 under the approval of the local ethical committee. RESULTS: The mean age of the 59 patients (47 females, 12 males) taking EGFR inhibitors was 52.4 ± 12.0 (range: 29-84). Forty-five patients had early stage and 14 patients had advanced stage carcinoma. Fourteen patients had colorectal carcinoma, three patients had renal cancer, and 42 patients had breast cancer. Forty-two patients were using trastuzumab (single therapy in 29 patients and combined therapy in 13 patients), five patients were using cetuximab, three patients were using sunitinib, eight patients were using panitumumab, and six patients were using pertuzumab. In 22 patients, PPL side effects were observed in the skin; it was G1 in 19 patients and G2 in three patients. In seven patients who developed acneiform side effects, systemic doxycycline was used, and in others, topical tetracycline and clindamycin were used. Except for one patient using trastuzumab, all patients has lesions on the face, upper trunk, and back. One patient exhibited an atypical rash, which was diagnosed as a granulomatous follicular reaction. Xerosis was present in two cases, and paronychia, pyogenic granuloma, trichomegaly, and madarosis were observed in one patient each. The patients who developed an acneiform rash were treated with topical and systemic antibiotics, light keratolytics, and emollients. The skin side effects of all patients were mild to moderate, and all patients completed the chemotherapy process. An acneiform skin rash and other dermatological side effects are common with EGFR inhibitors. To treat these side effects, emollients, topical steroids, and local, systemic antibiotics are recommended. Clindamycin may be preferred as a topical treatment, and doxycycline may be preferred as a systematic treatment.


Subject(s)
Antineoplastic Agents/adverse effects , Protein Kinase Inhibitors/adverse effects , Skin Diseases/chemically induced , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Colorectal Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Female , Humans , Kidney Neoplasms/drug therapy , Male , Middle Aged , Prospective Studies
13.
Postepy Dermatol Alergol ; 36(5): 609-615, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31839779

ABSTRACT

INTRODUCTION: Behcet's disease (BD) is a chronic inflammatory and multisystem vasculitis. Cardiac involvement is one of the major complications of BD. Cardiac involvement is sporadic in terms of its specific relationship to mortality. How to identify and follow up on cardiac-related complications in BD patients has yet to be determined. AIM: The aim of our study is to assess cardiovascular diseases in BD patients by measuring metabolic function and copeptin levels and comparing these to a healthy control group. Knowing the specific metabolic functions that are negatively affected by BD will help doctors determine which functions need to be more closely monitored in BD patients. Our study is the first study in the available literature that evaluates copeptin in BD patients. MATERIAL AND METHODS: A control group of 58 healthy volunteers, including 32 females and 26 males (average age: 39.8 ±10.3 years, range: 18-50 years), was formed to compare with 84 BD patients (average age: 40.5 ±11 years, range: 21-63 years), including 39 females and 45 males. Diastolic and systolic blood pressure, height, weight, body mass index (BMI), and waistline were measured for both groups. All study patients were also given hemograms, and fasting blood sugar (FBS), uric acid, lipid profile, insulin, C-reactive protein (CRP), and copeptin levels were measured. An ELISA Kit was used to measure copeptin. RESULTS: FBS, CRP, and insulin levels were significantly higher in the patient group (p < 0.001, p = 0.004, and p = 0.038, respectively). Patients who had had the disease for more than 10 years had higher BMIs, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels (p = 0.034, p = 0.004, p = 0.016, and p = 0.045, respectively). Additionally, CRP levels were found to be higher in long-term patients and patients with active lesions. Diastolic blood pressure and waist circumference were also higher in the BD group. Patients who had active lesions had significantly higher diastolic blood pressure (p = 0.047). There were no statistically significant differences in copeptin levels between BD and control groups. CONCLUSIONS: Cardiovascular involvement rarely contributes to the high mortality rate of BD patients. There were meaningful elevations in metabolic markers identified when BD and cardiovascular disease risk was assessed with metabolic parameters. The cardiac disease risk should be closely followed using metabolic functions, particularly in long-term BD patients with vascular involvement.

15.
São Paulo med. j ; 137(1): 96-99, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-1004742

ABSTRACT

ABSTRACT CONTEXT: Localized scleroderma (morphea) is characterized by fibrosis of skin and subcutaneous tissue. Granuloma annulare is a relatively common disease that is characterized by dermal papules and arciform plaques. CASE REPORT: Here, we present the case of a 42-year-old woman who developed granuloma annulare on the dorsum of her feet and abdominal region, and morphea on the anterior side of her lower limbs. We also discuss the etiological and pathogenetic processes that may cause the rare coexistence of these two diseases. CONCLUSION: Only a few cases in the literature have described coexistence of morphea and granuloma annulare.


Subject(s)
Humans , Female , Adult , Scleroderma, Localized/diagnosis , Granuloma Annulare/diagnosis , Scleroderma, Localized/complications , Scleroderma, Localized/pathology , Granuloma Annulare/complications , Granuloma Annulare/pathology , Rare Diseases
16.
Sao Paulo Med J ; 137(1): 96-99, 2019.
Article in English | MEDLINE | ID: mdl-29166431

ABSTRACT

CONTEXT: Localized scleroderma (morphea) is characterized by fibrosis of skin and subcutaneous tissue. Granuloma annulare is a relatively common disease that is characterized by dermal papules and arciform plaques. CASE REPORT: Here, we present the case of a 42-year-old woman who developed granuloma annulare on the dorsum of her feet and abdominal region, and morphea on the anterior side of her lower limbs. We also discuss the etiological and pathogenetic processes that may cause the rare coexistence of these two diseases. CONCLUSION: Only a few cases in the literature have described coexistence of morphea and granuloma annulare.


Subject(s)
Granuloma Annulare/diagnosis , Scleroderma, Localized/diagnosis , Adult , Female , Granuloma Annulare/complications , Granuloma Annulare/pathology , Humans , Rare Diseases , Scleroderma, Localized/complications , Scleroderma, Localized/pathology
18.
Am J Med Genet A ; 173(7): 1919-1921, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28449251

ABSTRACT

Vascular twin nevi (VTN) are characterized by the simultaneous dermatological manifestatiton of a telangiectatic naevus close to a nevus anemicus. Nevus anemicus (NA) is a vascular anomaly characterized by localized pale patches with normal melanine and melanocyte level. According to twin spotting phenomenon crossing-over in heterozygous somatic-cells during mitosis results in two different offspring homozygous cells. Consequent to this mechanism, two different vascular anomalies may occur at the same region. We present a patient with VTN and NA combination which we think serves as an example for a rare twin spotting phenomenon in the literature.

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