Challenges and Opportunities in Dermatology

Special Issue:

Challenges and Opportunities in Dermatology

Kadircan H. Keskinbora, PhD
Professor of Ophthalmology, Ph. D., History of Medicine and Medical Ethics, Bahçeşehir University, School of Medicine, Istanbul, Turkiye

Eda Kumbasar
Specialist on Dermatology and Cosmetology, Private Clinic, Istanbul, Turkiye

Abstract

Our aim in this article is to consider ethical concerns and sensitivities in Dermatology and Cosmetic applications. It is appropriate for dermatologists to make cosmetic applications and use artificial intelligence aid as experts who know the structure and diseases of the skin best. The practice of cosmetology by physicians other than dermatologists creates ethical problems.

 

Women are especially more interested in dermatology. Body dysmorphic disorders are more common in women. When dermatologists evaluate the cosmetic dermatology patient and create a treatment plan, if there are unrealistic expectations, the patient should be guided correctly by considering the patient’s wishes. Social media applications, which have attracted attention in recent years, have caused an increase in body dysmorphic disorders in individuals.

 

Cosmetology is a division that can never be separated from dermatology. Patients frequently apply to cosmetic dermatology because of hyperpigmentation problems, aging problems, hair problems, toxin applications, dermal filler procedures, chemical peels, and mesotherapy, and ablative laser procedures. Burns resulting from laser epilation applications performed in aesthetic centers, complications such as tissue necrosis caused by dermal filler procedures performed by non-physicians, cosmetic problems, soft tissue infections, and allergic reactions resulting from applications such as mesotherapy and platelet-rich plasma are diseases frequently seen in dermatology outpatient clinics.

 

Another important issue is the materials used in platelet-rich plasma, mesotherapy, toxin application, and dermal filler applications must be in the Class 3 Medical device category. Patients who apply to clinics for treatment should be made aware of this issue and patients should be protected from the complications that these medications may cause. Physicians should not use products that do not have class 3 certificates in cosmetic dermatology to keep the cost of the product low, especially when choosing materials.

 

In medicine, there is always an aesthetic concern beyond technical or even scientific concerns. We think that it is necessary to express and elaborate on the concerns arising from the ethical issues that are experienced or may be experienced in dermatology practices. Physicians always try to take the patient’s psychological and pathological problems into consideration. However, ethical concerns should not be forgotten when treating the field of aesthetics.

Kadircan H. Keskinbora, MD, PhD
Professor of Ophthalmology, Ph.D., History of Medicine, and Medical Ethics, Bahçeşehir University, School of Medicine, Istanbul, Turkiye ORCID No. 0000-0003-1940-1026Professor of Ophthalmology, Ph.D., History of Medicine, and Medical Ethics, Bahçeşehir University, School of Medicine, Istanbul, Turkiye ORCID No. 0000-0003-1940-1026

Eda Kumbasar, MD
Specialist in Dermatology and Cosmetology, Private Clinic, Istanbul, Turkiye ORCID 0000-0001-5789-6301

Abstract

Dermatology has gradually changed over the past few decades with the advances of Artificial Intelligence (AI) in the field of medicine. However, the application of Artificial intelligence in clinical practice remains a challenge.

When using Artificial intelligence in the dermatology practice, it is extremely important to consider not only the diagnosis and treatment of patients but also medical ethics details. This article reveals that there may be ethical difficulties when using Artificial intelligence in the field of dermatology and addresses the challenges related to ethical problems that Artificial intelligence may have caused in dermatological practices in recent years.  Artificial intelligence in medicine and dermatology causes challenges related to ethics and transparency. There are ethical problems, risks, and potential harms associated with the unexamined use of Artificial intelligence and machine learning when applied to health information and services.

Studies have shown that Artificial intelligence can diagnose skin lesions using clinical and dermoscopic images with accuracy that is on par with or better than dermatologists. As a result, Artificial intelligence is becoming a more significant tool in dermatology. 

Advances in artificial technology improve diagnostic precision and enable early illness assessment.  The accuracy rate of artificial intelligence systems used in skin cancer diagnosis is almost the same as dermatologists.

However, there is still a dearth of clinical validation in the actual world. In this article, deep learning applications in dermatology are examined, which is the state-of-the-art, artificial intelligence technology for image analysis. We also assess the technology’s present limitations, possible points of failure, difficulties with performance measurement, interpretability, and ethical issues. It is crucial to take into account medical ethics in addition to patient diagnosis and treatment when implementing Artificial intelligence in dermatology practices. This article discusses the ethical issues that Artificial intelligence may have raised in dermatological practices in the recent past and indicates that there might be moral dilemmas when applying Artificial Intelligence in this field. 

Giulia Ciccarese, MD, PhD
Dermatology Clinic, Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10 16132, Genoa, Italy

Francesco Drago, MD
Dermatology Clinic, Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10 16132, Genoa, Italy; DI.S.Sal., Section of Dermatology, University of Genoa, Via Pastore, 1, 16132, Genoa, Italy

Bianco Drago, MD
Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy

Aurora Parodi, MD
Dermatology Clinic, Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10 16132, Genoa, Italy; DI.S.Sal., Section of Dermatology, University of Genoa, Via Pastore, 1, 16132, Genoa, Italy

Abstract

In the last two decades, there has been a resurgence of syphilis worldwide. However, epidemiological data on neurosyphilis are inconsistent for the lack of reporting data and diagnostic gold standard tests. The aim of the present study was to estimate the prevalence of syphilis reactivity in a cohort of patients with neurological diseases of our hospital. We retrospectively analyzed the medical records of the patients hospitalized at the Stroke Unit of the Neurology Clinic and those suffering from cognitive impairment hospitalized at the acute ward of the Geriatrics Clinic between January 2017 and December 2019. Also the patients who attended the Movement disorder outpatient clinic during the same study period were examined. To detect syphilis reactivity a qualitative specific treponemal test on patient’s serum was performed: the Treponema pallidum haemagglutination assay (TPHA). A total of 652 patients were admitted and 315 of them (52%) were submitted to a routine screening for syphilis: 307 (97%) were negative while 8 (3%) had a positive syphilis serology. The TPHA-positive patients (4 males, 4 females) were 2 patients with stroke, 5 with cognitive impairment and 1 with Parkinsonism with a mean age of 83 years, suffering from multiple comorbidities. Although the patients we have retrospectively studied have not undergone lumbar puncture to confirm the diagnosis of neurosyphilis, the not negligible syphilis reactivity rate found in our series suggests that serological screening for syphilis should be reviewed as a routine screening test in neurology and geriatrics departments, especially if the clinical presentation of the neurological diseases is atypical.

Daniel Barolet, MD FRCPC
McGill University

Abstract

Photobiomodulation (PBM), the therapeutic use of low intensity light, typically in the visible and infrared (IR) wavelengths, has been demonstrated to be efficacious in the treatment and prevention of numerous skin conditions. The PBM biological response begins with chromophores, photon accepting molecules which convert light into signals that can stimulate certain biological processes. Important chromophores initiating the PBM response are Cytochrome C Oxidase (CCO), with absorption peaks in the red and near IR wavelengths, opsins absorbing blue and green wavelengths and intracellular water acting at specific sites in the cell. PBM can activate cell signaling processes. The increase in electron transport, oxygen consumption, mitochondrial membrane potential, and ATP synthesis, particularly in hypoxic or stressed cells, can lead to the up-regulation of cell repair and survival pathways. In PBM, the light delivery parameters which maximize the therapeutic response are defined within specific ranges, with total fluence and irradiance being of particular importance. PBM emerges as a valuable complementary treatment modality in dermatology. In terms of tissue repair, wound healing is accelerated by PBM. Cutaneous wounds, erosive mucositis in oncology, leg ulcers, as well as burns and radiodermatitis all benefit from PBM treatment. Widely used to accelerate healing after aggressive aesthetic treatments, PBM reduces inflammation following treatments like skin resurfacing, vascular and benign pigmented lesions, or chemical peels. It has also been shown to be effective in treating dyspigmentation. In the case of hyperpigmentation, melanin synthesis is inhibited with IR light. Additionally, PBM has shown benefits in the treatment of acne, prevention and treatment of hypertrophic scars. It has shown promise in skin rejuvenation, the treatment of alopecia, cellulite, as well as other skin diseases. The discovery of new applications for PBM, already an effective form of treatment and prevention for many skin conditions, is continually expanding.

Chutika Srisuttiyakorn, M.D.
1 Division of Dermatology, Department Of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

Patcharasiri Bocam, M.D.
1 Division of Dermatology, Department Of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

Abstract

Background: Hypopigmented mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. Although the prognosis of hypopigmented mycosis fungoides is excellent, the diagnosis is usually missed.

Objective: The study aimed to identified the prevalence of patients with hypopigmented mycosis fungoides presenting hypopigmentation in Phramongkutklao Hospital, Bangkok, Thailand. We also reported the characteristic of hypopigmented mycosis fungoides among patients presenting hypopigmentation and compared clinical presentations between patients with a diagnosis of hypopigmented mycosis fungoides and patients with other diagnoses

Materials and Methods: We conducted a retrospective among 56 patients presenting hypopigmentation and receiving skin biopsies at Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand between January 2016 to December 2021. The data parameters including demographic data, clinical manifestations (symptoms, size and morphology of the lesions, e.g., scale, margin, erythema, atrophy, mottled hypopigmentation, involved body surface area and distribution, histopathologic reports, special stains, final diagnosis, further investigations, treatments, follow-up duration and result of the treatments were recorded.

Results: The prevalence of hypopigmented mycosis fungoides among patient presenting with hypopigmentation was 16.1%. Compared with patients with other diagnoses, patients with hypopigmented mycosis fungoides usually had lesions with ill-defined margins (P-value=0.045) and presence of atrophy lesion (P-value=0.023).

Conclusion: The prevalence of hypopigmented mycosis fungoides involved 16.1% of patients presenting hypopigmentation. The presence of ill-defined margins and atrophic lesions led to suspected hypopigmented MF in our study. This data could be useful in epidemiologic information and might be adapted when choosing lesions for biopsy to diagnose MF.

Emily E Dando, MD
Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, PA

Misha Rosenbach, MD
Department of Dermatology, University of Pennsylvania, Philadelphia, PA

Joseph C English III, MD
Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, PA

Abstract

Granulomatous drug reactions have been associated with many medications, including targeted therapeutics such as biologics and small molecule inhibitors. The four main clinicopathologic reaction patterns are drug-induced sarcoidosis-like reaction, reactive granulomatous dermatitis, granuloma annulare, and accelerated rheumatoid nodulosis. These reactions often develop months after exposure to the causative medication and clinically can mimic other granulomatous diseases or metastatic cancer, which may be differentiated with biopsy, tissue culture, and radiographic imaging. Granulomatous inflammation may be limited to the skin, where early recognition helps to facilitate diagnosis. Cutaneous manifestations vary by reaction pattern, ranging from erythema nodosum-like lesions to painful rheumatoid nodules to annular indurated plaques. Systemic granulomatous inflammation is typically only observed in sarcoidosis-like reaction or accelerated rheumatoid nodulosis and most often involves the lungs or lymph nodes. Targeted therapeutics implicated in granulomatous drug reactions are TNFα inhibitors, BRAF and MEK inhibitors, immune checkpoint inhibitors and, to a lesser extent, other cytokine modulators. TNFα inhibitors, in particular, are among the most common drugs in any class associated with the four primary granulomatous drug eruptions. We review the current literature on granulomatous reactions to these agents, including proposed mechanisms and the range of clinical manifestations. Management may include drug discontinuation, topical therapy, or systemic immunosuppression depending on the severity of the granulomatous drug reaction. In the setting of malignancy, granulomatous inflammation does not appear to be of prognostic value, although more studies are needed. 

Frederick H. Silver
Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, NJ 08854; OptoVibronex, LLC., Allentown, Pa

Tanmay Deshmukh
OptoVibronex, LLC., Allentown, Pa

Nicole Ryan
Dermatology, Summit Health, Berkeley Heights NJ 07922

Arielle Romm
Dermatology, Summit Health, Berkeley Heights NJ 07922

Hari Nadiminti
Dermatology, Summit Health, Berkeley Heights NJ 07922

Abstract

Vibrational optical coherence tomography (VOCT) has been used to non-invasively measure the resonant frequency and elastic modulus of different types of BCCs to compare the physical biomarker characteristics of each of these lesions. The results suggest that in very small lesions (about 0.05 mm in diameter) new 80Hz and 130Hz resonant frequency peaks are seen not present in normal skin or in healing wounds. In all other BCCs, new 80Hz, 130Hz and 260Hz resonant frequency peaks are found like those found in other carcinomas including SCC and melanoma.

Small BCCS are characterized by new 80Hz and 130Hz in the absence of a significant 50Hz peak unlike actinic keratoses that are characterized by 50Hz, 80Hz and 130Hz peaks. In the absence of the 260Hz peak, small BCCs appear to be a precursor to larger BCCs. Pigmented BCCs exhibit a larger ratio of the 50Hz/80Hz peaks compared to the other BCC types in addition to peaks at 130Hz and 260Hz suggesting that benign melanocyte lesions contribute to the 50 Hz peak. Further studies are needed to understand the factors that drive differences in shape and invasiveness of cancerous BCCs.

While all BCCs were found to contain new cell and blood vessel resonant frequencies that coincide with fibrotic tissue encapsulating the tumors in the papillary dermis, other factors must drive differences in the shape and invasiveness of the different BCCs. It is hypothesized that the new cells and blood vessels formed lead to the deposition of fibrous tissue in all BCCs and is partially driven by an epithelial-mesenchyme transition. It is concluded that fibrotic tissue is found encapsulating all cancerous BCCs and that this layer of tissue may limit invasiveness and metastatic behavior of this tumor type. In general, tumor shape and invasiveness are likely influenced by the exact cellular mutations in each lesion type and the extent of UV light damage experienced by the surrounding extracellular matrix.

Gang Zhou
1. Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro-oncology 2013; 15 Suppl 2: ii1-56. Doi: 10.1093/neuonc/not151. 2. Thakkar JP, Dolecek TA, Horbinski C, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2014; 23: 1985-1996. DOI: 10.1158/1055-9965.EPI-14-0275. 3. Korja M, Raj R, Seppa K, et al. Glioblastoma survival is improving despite increasing incidence rates: a nationwide study between 2000 and 2013 in Finland. Neuro-oncology 2019; 21: 370-379. Doi: 10.1093/neuonc/noy164. 4. Miranda-Filho A, Pineros M, Soerjomataram I, et al. Cancers of the brain and CNS: global patterns and trends in incidence. Neuro-oncology 2017; 19: 270-280. Doi: 1093/neuonc/now166. 5. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England journal of medicine 2005; 352: 987-996. Doi: 10.1056/NEJMoa043330. 6. Visser O, Ardanaz E, Botta L, et al. Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study. European journal of cancer 2015; 51: 2231-2241. DOI: 10.1016/j.ejca.2015.07.032. 7. Davis L. Spongioblastoma Multiforme of the Brain. Ann Surg 1928; 87: 8-14. 8. Pasquier B, Pasquier D, N’Golet A, et al. Extraneural metastases of astrocytomas and glioblastomas: clinicopathological study of two cases and review of literature. Cancer 1980; 45: 112-125. 9. Anzil AP. Glioblastoma multiforme with extracranial metastases in the absence of previous craniotomy. Case report. Journal of neurosurgery 1970; 33: 88-94. Doi: 10.3171/jns.1970.33.1.0088. 10. Anghileri E, Castiglione M, Nunziata R, et al. Extraneural metastases in glioblastoma patients: two cases with YKL-40-positive glioblastomas and a meta-analysis of the literature. Neurosurgical review 2016; 39: 37-45; discussion 45-36. Doi: 10.1007/s10143-015-0656-9. 11. Schweitzer T, Vince GH, Herbold C, et al. Extraneural metastases of primary brain tumors. Journal of neuro-oncology 2001; 53: 107-114. DOI: 10.1023/a:1012245115209. 12. Hoffman HJ and Duffner PK. Extraneural metastases of central nervous system tumors. Cancer 1985; 56: 1778-1782. DOI: 10.1002/1097-0142(19851001)56:7+<1778::aid-cncr2820561309>3.0.co;2-i. 13. Figueroa P, Lupton JR, Remington T, et al. Cutaneous metastasis from an intracranial glioblastoma multiforme. Journal of the American Academy of Dermatology 2002; 46: 297-300. DOI: 10.1067/mjd.2002.104966. 14. Lun M, Lok E, Gautam S, et al. The natural history of extracranial metastasis from glioblastoma multiforme. Journal of neuro-oncology 2011; 105: 261-273. DOI: 10.1007/s11060-011-0575-8. 15. Han SR, Yoon SW, Yee GT, et al. Extraneural metastases of anaplastic oligodendroglioma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2008; 15: 946-949. Doi: 10.1016/j.jocn.2006.09.013. 16. Piccirilli M, Brunetto GM, Rocchi G, et al. Extra central nervous system metastases from cerebral glioblastoma multiforme in elderly patients. Clinico-pathological remarks on our series of seven cases and critical review of the literature. Tumori 2008; 94: 40-51. Doi: 10.1177/030089160809400109. 17. Romero-Rojas AE, Diaz-Perez JA, Amaro D, et al. Glioblastoma metastasis to parotid gland and neck lymph nodes: fine-needle aspiration cytology with histopathologic correlation. Head and neck pathology 2013; 7: 409-415. Doi: 10.1007/s12105-013-0448-x. 18. Huang P, Allam A, Taghian A, et al. Growth and metastatic behavior of five human glioblastomas compared with nine other histological types of human tumor xenografts in SCID mice. Journal of neurosurgery 1995; 83: 308-315. Doi: 10.3171/jns.1995.83.2.0308. 19. Zustovich F, Della Puppa A, Scienza R, et al. Metastatic oligodendrogliomas: a review of the literature and case report. Acta neurochirurgica 2008; 150: 699-702; discussion 702-693. DOI: 10.1007/s00701-008-1507-z. 20. Tuettenberg J, Grobholz R, Korn T, et al. Continuous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. Journal of cancer research and clinical oncology 2005; 131: 31-40. Doi: 10.1007/s00432-004-0620-5. 21. Taha M, Ahmad A, Wharton S, et al. Extra-cranial metastasis of glioblastoma multiforme presenting as acute parotitis. British journal of neurosurgery 2005; 19: 348-351. DOI: 10.1080/02688690500305506. 22. Kraft M, Lang F, Braunschweig R, et al. Parotid gland metastasis from glioblastoma multiforme: a case report and review of the literature. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies 2008; 265: 709-711. DOI: 10.1007/s00405-007-0499-2. 23. Frank S, Kuhn SA, Brodhun M, et al. Metastatic glioblastoma cells use common pathways via blood and lymphatic vessels. Neurologia i neurochirurgia polska 2009; 43: 183-190. 24. Mentrikoski M, Johnson MD, Korones DN, et al. Glioblastoma multiforme in skin: a report of 2 cases and review of the literature. The American Journal of dermatopathology 2008; 30: 381-384. Doi: 10.1097/DAD.0b013e31817532c4. 25. Gururangan S, McLaughlin CA, Brashears J, et al. Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma. Journal of neuro-oncology 2006; 77: 207-212. DOI: 10.1007/s11060-005-9029-5. 26. Nager GT. Gliomas involving the temporal bone clinical and pathological aspects. The Laryngoscope 1967; 77: 454-488. Doi: 10.1288/lary.1967.000770403. 27. M T, Stephenson, Corinne, Y, Shan, Bui, Marilyn. Cytological Diagnosis of Extracranial Extension of Glioblastoma to Scalp. ASCP Case Reports 2013; 41: 13140. DOI: 2.1.3466.3041. 28. McGovern PC, Lautenbach E, Brennan PJ, et al. Risk factors for postcraniotomy surgical site infection after 1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer placement. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2003; 36: 759-765. Doi: 10.1086/368082. 29. Shi M and Sanche L. Convection-Enhanced Delivery in Malignant Gliomas: A Review of Toxicity and Efficacy. Journal of oncology 2019; 2019: 9342796. Doi: 10.1155/2019/9342796. 30. Duffy PE, Graf L and Rapport MM. Identification of glial fibrillary acidic protein by the immunoperoxidase method in human brain tumors. Journal of neuropathology and experimental neurology 1977; 36: 645-652. Doi: 10.1097/00005072-197707000-00001. 31. Stoyanov GS, Petkova L, Iliev B, et al. Extracranial Glioblastoma Metastasis: A Neuropathological Case Report. Cureus 2023; 15: e35803. Doi: 10.7759/cureus.35803. 32. Ogungbo BI, Perry RH, Bozzino J, et al. Report of GBM metastasis to the parotid gland. Journal of neuro-oncology 2005; 74: 337-338. DOI: 10.1007/s11060-005-1480-9. 33. Alhoulaiby S, Abdulrahman A, Alouni G, et al. Extra-CNS metastasis of glioblastoma multiforme to cervical lymph nodes and parotid gland: A case report. Clinical case reports 2020; 8: 1672-1677. Doi: 10.1002/ccr3.2985. 34. Swinnen J, Gelin G, Fransis S, et al. Glioblastoma with extracranial parotid, lymph node, and pulmonary metastases: a case report. Radiology case reports 2019; 14: 1334-1347. Doi: 10.1016/j.radcr.2019.08.011. 35. Schwock J, Mirham L and Ghorab Z. Cytology of Extraneural Metastases of Nonhematolymphoid Primary Central Nervous System Tumors: Six Cases with Histopathological Correlation and Literature Update. Acta cytologica 2021; 65: 529-540. Doi: 10.1159/000517480.

Tao L Wan
1. Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro-oncology 2013; 15 Suppl 2: ii1-56. Doi: 10.1093/neuonc/not151. 2. Thakkar JP, Dolecek TA, Horbinski C, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2014; 23: 1985-1996. DOI: 10.1158/1055-9965.EPI-14-0275. 3. Korja M, Raj R, Seppa K, et al. Glioblastoma survival is improving despite increasing incidence rates: a nationwide study between 2000 and 2013 in Finland. Neuro-oncology 2019; 21: 370-379. Doi: 10.1093/neuonc/noy164. 4. Miranda-Filho A, Pineros M, Soerjomataram I, et al. Cancers of the brain and CNS: global patterns and trends in incidence. Neuro-oncology 2017; 19: 270-280. Doi: 1093/neuonc/now166. 5. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England journal of medicine 2005; 352: 987-996. Doi: 10.1056/NEJMoa043330. 6. Visser O, Ardanaz E, Botta L, et al. Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study. European journal of cancer 2015; 51: 2231-2241. DOI: 10.1016/j.ejca.2015.07.032. 7. Davis L. Spongioblastoma Multiforme of the Brain. Ann Surg 1928; 87: 8-14. 8. Pasquier B, Pasquier D, N’Golet A, et al. Extraneural metastases of astrocytomas and glioblastomas: clinicopathological study of two cases and review of literature. Cancer 1980; 45: 112-125. 9. Anzil AP. Glioblastoma multiforme with extracranial metastases in the absence of previous craniotomy. Case report. Journal of neurosurgery 1970; 33: 88-94. Doi: 10.3171/jns.1970.33.1.0088. 10. Anghileri E, Castiglione M, Nunziata R, et al. Extraneural metastases in glioblastoma patients: two cases with YKL-40-positive glioblastomas and a meta-analysis of the literature. Neurosurgical review 2016; 39: 37-45; discussion 45-36. Doi: 10.1007/s10143-015-0656-9. 11. Schweitzer T, Vince GH, Herbold C, et al. Extraneural metastases of primary brain tumors. Journal of neuro-oncology 2001; 53: 107-114. DOI: 10.1023/a:1012245115209. 12. Hoffman HJ and Duffner PK. Extraneural metastases of central nervous system tumors. Cancer 1985; 56: 1778-1782. DOI: 10.1002/1097-0142(19851001)56:7+<1778::aid-cncr2820561309>3.0.co;2-i. 13. Figueroa P, Lupton JR, Remington T, et al. Cutaneous metastasis from an intracranial glioblastoma multiforme. Journal of the American Academy of Dermatology 2002; 46: 297-300. DOI: 10.1067/mjd.2002.104966. 14. Lun M, Lok E, Gautam S, et al. The natural history of extracranial metastasis from glioblastoma multiforme. Journal of neuro-oncology 2011; 105: 261-273. DOI: 10.1007/s11060-011-0575-8. 15. Han SR, Yoon SW, Yee GT, et al. Extraneural metastases of anaplastic oligodendroglioma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2008; 15: 946-949. Doi: 10.1016/j.jocn.2006.09.013. 16. Piccirilli M, Brunetto GM, Rocchi G, et al. Extra central nervous system metastases from cerebral glioblastoma multiforme in elderly patients. Clinico-pathological remarks on our series of seven cases and critical review of the literature. Tumori 2008; 94: 40-51. Doi: 10.1177/030089160809400109. 17. Romero-Rojas AE, Diaz-Perez JA, Amaro D, et al. Glioblastoma metastasis to parotid gland and neck lymph nodes: fine-needle aspiration cytology with histopathologic correlation. Head and neck pathology 2013; 7: 409-415. Doi: 10.1007/s12105-013-0448-x. 18. Huang P, Allam A, Taghian A, et al. Growth and metastatic behavior of five human glioblastomas compared with nine other histological types of human tumor xenografts in SCID mice. Journal of neurosurgery 1995; 83: 308-315. Doi: 10.3171/jns.1995.83.2.0308. 19. Zustovich F, Della Puppa A, Scienza R, et al. Metastatic oligodendrogliomas: a review of the literature and case report. Acta neurochirurgica 2008; 150: 699-702; discussion 702-693. DOI: 10.1007/s00701-008-1507-z. 20. Tuettenberg J, Grobholz R, Korn T, et al. Continuous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. Journal of cancer research and clinical oncology 2005; 131: 31-40. Doi: 10.1007/s00432-004-0620-5. 21. Taha M, Ahmad A, Wharton S, et al. Extra-cranial metastasis of glioblastoma multiforme presenting as acute parotitis. British journal of neurosurgery 2005; 19: 348-351. DOI: 10.1080/02688690500305506. 22. Kraft M, Lang F, Braunschweig R, et al. Parotid gland metastasis from glioblastoma multiforme: a case report and review of the literature. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies 2008; 265: 709-711. DOI: 10.1007/s00405-007-0499-2. 23. Frank S, Kuhn SA, Brodhun M, et al. Metastatic glioblastoma cells use common pathways via blood and lymphatic vessels. Neurologia i neurochirurgia polska 2009; 43: 183-190. 24. Mentrikoski M, Johnson MD, Korones DN, et al. Glioblastoma multiforme in skin: a report of 2 cases and review of the literature. The American Journal of dermatopathology 2008; 30: 381-384. Doi: 10.1097/DAD.0b013e31817532c4. 25. Gururangan S, McLaughlin CA, Brashears J, et al. Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma. Journal of neuro-oncology 2006; 77: 207-212. DOI: 10.1007/s11060-005-9029-5. 26. Nager GT. Gliomas involving the temporal bone clinical and pathological aspects. The Laryngoscope 1967; 77: 454-488. Doi: 10.1288/lary.1967.000770403. 27. M T, Stephenson, Corinne, Y, Shan, Bui, Marilyn. Cytological Diagnosis of Extracranial Extension of Glioblastoma to Scalp. ASCP Case Reports 2013; 41: 13140. DOI: 2.1.3466.3041. 28. McGovern PC, Lautenbach E, Brennan PJ, et al. Risk factors for postcraniotomy surgical site infection after 1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer placement. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2003; 36: 759-765. Doi: 10.1086/368082. 29. Shi M and Sanche L. Convection-Enhanced Delivery in Malignant Gliomas: A Review of Toxicity and Efficacy. Journal of oncology 2019; 2019: 9342796. Doi: 10.1155/2019/9342796. 30. Duffy PE, Graf L and Rapport MM. Identification of glial fibrillary acidic protein by the immunoperoxidase method in human brain tumors. Journal of neuropathology and experimental neurology 1977; 36: 645-652. Doi: 10.1097/00005072-197707000-00001. 31. Stoyanov GS, Petkova L, Iliev B, et al. 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Bing Leng
Department of Pathology, Baylor Scott & White Health, 2401 S. 31st. St. MS-01-266 Temple, TX 76508

Frank Yuan Shan
Department of Pathology, Baylor Scott & White Health, 2401 S. 31st. St. MS-01-266 Temple, TX 76508

Abstract

Glioblastoma multiforme (GBM) is a WHO grade 4 primary brain tumor with a recalcitrant and dismal prognosis and a 14-month-median survival time. The extracranial spread of GBM is so rare that historically it was not believed to spread outside of the central nervous system (CNS). Since the first extracranial spread of GBM was described in 1928, more cases have been reported. However, the mechanisms have yet to be elucidated due to the rareness of well-documented cases. Here, we reported two cases of GBM with postoperative extracranial spread and reviewed related literature.

V.J. Sebastian Criton, MD, HOD
Department of Dermatology, Amala Institute of Medical Sciences, Thrissur, Kerala, India

Joy Sanjana, MBBS
Junior resident, Department of Dermatology, Amala Institute of Medical Sciences, Thrissur, Kerala, India

Abstract

Millions worldwide, particularly children, suffer from the prevalent inflammatory skin condition known as Atopic Dermatitis (AD), with its prevalence on a constant rise.It’s impact extends beyond affecting merely the skin, contributing towards more complex health problems. The exact cause of this condition is multifactorial: genetic, environmental and immunologic factors all play significant roles; however, attention has recently focused on the role gut microbiota may have in relation to ‘gut-skin’ axis disturbances. Gut microbiota imbalances may be influenced by diet, antibiotic use as well as changes in environmental conditions that may contribute to Atopic Dermatits pathogenesis.  New research concentrates on therapies including probiotics, prebiotics and faecal microbiota transplantation. Multi-strain probiotic formulas in particular, are promising; such products have shown to potentially help manage Atopic Dermatitis symptoms by altering the immune response and adjusting the composition of gut microbes. The available evidence also suggests that exclusion diets can be tailored to serve as a form of dietary management. Fecal microbiota transplantation represents an innovative approach that requires additional scrutiny regarding its efficacy and safety in treating Atopic Dermatitis. The complex relationship between skin barrier function, immune responses and gut microbial composition offers possibilities for developing novel therapies targeting the microbiome in Atopic Dermatitis management.

Wen Liu
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Uppsala University, Uppsala, Sweden

Mark Gonn
Unit of Internal Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Susanna von Holst
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Jessada Thutkawkorapin
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Xiang Jiao
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Jan Björk2
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Gastroenterology section, medical unit Gastroenterology, Rheumatology and Dermatology, Karolinska University hospital, Stockholm, Sweden

Ann-Sofie Backman
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden: Gastroenterology section, medical unit Gastroenterology, Rheumatology and Dermatology, Karolinska University hospital, Stockholm, Sweden

Kristina Lagerstedt-Robinson
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

Annika Lindblom
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

Abstract

Colorectal cancer (CRC) is a multifactorial disease, where both the environment and genetics play a role. It is estimated that approximately 35% of CRCs have a potentially identifiable genetic cause. Well-known and highly penetrant genetic causes make up less than 5% of all CRC, and leave many families not explained by known predisposing genes/mutations. Low penetrant alleles have also been thought to modify the risk of CRC. Linkage studies have been successful in discovering and localizing highly penetrant genes in CRC and risk loci has become possible to discover performing genome wide association studies (GWAS).

In this study we have analyzed families with CRC where individuals with CRC as well as individuals with premalignant lesions, adenomas, were codes as affected. In total 600 individuals in 121 families were included in the study.

In total three genomic regions were found with suggestive linkage located at 4p16.3, 6p24.3 and 10p14. These regions were further studied using sequencing analysis and association studies using haplotypes.

Anne Braae Olesen, MD, PhD
Ass Prof Department of Dermatology, Aarhus University Hospital , Palle Juul-Jensens Boulevard 67, DK-8200 Aarhus N

Simon Fage, MD
Department of Dermatology, Aarhus University Hospital, Palle Juul- Jensens Boulevard 67, DK-8200 Aarhus N

Abstract

Purpose
To describe our three year experience with intralesional injection of sodium thiosulphate as treatment for dystrophic calcification (DC) in patients suffering from Systemic Sclerosis (SSc), overlap syndrome and dermatomyositis.

Methods
Between September 2016 and October 2019, selected SSc, overlap syndrome, and dermatomyositis patients with problematic DC were systematically and prospectively recruited to treatment once a week for four weeks and follow up after 12-16 weeks. During each visit, data concerning DC size, ulceration, inflammation, and both patient and physician global score (1-10) (PtGA and PhGA) were collected on customized data sheets. The DC lesions were injected with sodium thiosulfate 150mg/ml on top or in the upper part of the lesion by the same clinician. After treatment, the lesion was covered up with a pressure distributing plaster for at least 24 hours.

Results
Among 43 patients offered treatment, 38 patients, 33 women and 5 men, had one or more problematic DC treated with intralesional sodium thiosulfate. The total number of treatments was 463. The patients had between 1 and &gt;200 DC lesions and at each session between 1 and 22 lesions were treated.

A total of 36 series consisting of 4 treatments were performed in 29 patients, 26 women and 3 men. Among these patients, 18 had systemic sclerosis of limited cutaneous type (lcSSc), 8, 2, and 1 patient had systemic sclerosis of diffuse cutaneous type (dcSSc), overlap syndrome, and dermatomyositis respectively.

The average PtGA and PhGA before treatment was 6.4 and 6.1 respectively. A significantly decrease of the average PtGA and PhGA score was observed week by week and after the third treatment the average decrease in PtGA and PhGA was 2.7 and 2.5 respectively (p&lt;&lt;0.001). Almost all patients experienced intense pain during and after injection (up to several minutes), but otherwise side effects were few and not serious.

Conclusions
We find that intralesional sodium thiosulfate injections have positive effect with limited side effects on selected SSc patients with problematic DC. We recognize the limitations of the study design leaving plenty of questions to be addressed. It is our clinical impression that both patient, lesion, and clinician related factors may influence the outcome of the treatment. We hope that our treatment regimen may inspire physicians to consider sodium thiosulfate injections as a possible treatment for troublesome DC before referring to surgical interventions.

Ali Al Kaissi
National Medical Research Center for Traumatology and Orthopedics n.a. G.A. Ilizarov, Kurgan, Russia

Sergey Ryabykh
Pirogov Russian National Research Medical University- Veltischev Clinical Institute, Moscow, Russia

Hamza Al Kaissi
IhreHaut Dermatology Center, Kaufbeuren, Bavaria – Germany

Vasileios Dougales
Department of orthopedic surgery and traumatology, Kantonsspital Aarau, Switzerland

Vladimir Kenis
Department of Foot and Ankle Surgery, Neuroorthopaedics and Systemic Disorders, Pediatric Orthopedic Institute n.a. H. Turner, Parkovaya str., 64-68, Pushkin, Saint Petersburg, Russia

Susanne Gerit Kircher
Department of Medical Patho- Chemistry and genetics, Medical University of Vienna, Austria

Franz Grill
Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria

Abstract

Background: Arthrogryposis multiplex congenita is the usual misdiagnosis given for children born with multiple joint dislocation syndromes. The purpose of the study was to refute the term arthrogryposis multiplex congenita as well as contractures and replace them with a precise diagnostic entity.

Methods: Eight unrelated children referred to our orthopaedic departments with the presumptive misdiagnosis of arthrogryposis multiplex because of multiple joint contractures. Five boys and three girls (aged 1 month-5 year) and one adult-15-year-old-boy have been included. We performed extensive clinical and radiographic phenotypic characterization of every single patient associated with confirmatory genotype. 

Results: We accomplished the diagnoses in all these children. Three diagnostic entities emerged. Larsen syndrome, diastrophic dysplasia and Escobar syndrome. The genotype has been performed accordingly.

Conclusion: The reason for presenting this study is threefold; Firstly, to illustrate the necessity of the etiological diagnosis in children with the misdiagnosis of arthrogryposis multiplex congenita in connection with the presumptive misdiagnosis of fetal akinesia, Pena-Shokeir syndrome or congenital myopathy. Secondly, full consideration of the phenotypic characterization and the additional pathological features allowed us to achieve proper management. Thirdly, is to clarify that excessive vigorous attempts to correct the dislocations in children with skeletal dysplasia were felt to not be recommended because of the risk of damaging the dysplastic epiphyses.

Claudio Roberto Bezerra-Santos
Associate Professor of Immunology, Department of Physiology and Pathology, Health Science Centre, Laboratory of Immunopharmacology, Federal University of Paraiba (UFPB), Joao Pessoa, Brazil

Esther Bastos Palitot
Professor of Dermatology, Head of Reference Service for Psoriasis, Federal University of Paraiba (UFPB), Medical Science Centre, LauroWanderley Hospital Ebserh/UFPB, Joao Pessoa, Brazil

Guilherme Bastos Palitot Brito
Resident Doctor, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil.

Alessandra de Sousa Braz
Professor of Rheumatology, Spondyloarthritis Clinic, Federal University of Paraiba (UFPB), Medical Science Centre, LauroWanderley Hospital Ebserh/UFPB, Joao Pessoa, Brazil

Abstract

Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease of the skin and joints still poorly understood in pediatric patients. It has been reported a case report of PsA in a male infant patient in Paraiba state, Northeast Brazil. The goal of this study was describing a rare case of juvenile PsA and its management upon using classical and biologic treatment based on the drug etanercept. The patient was diagnosed with scales on the scalp, knees and other parts of the body and joint inflammation besides social behavior deficit since he was aged 5. Classical therapy to PsA including acitretrin and topical glucocorticoids did not ameliorate the illness symptoms. Then, the patient received the anti-TNF-α drug etanercept used to treat moderate to severe psoriasis and juvenile rheumatoid arthritis. Before the week 16 of the treatment was observed a strong remission of the symptoms which is related to the inhibition of the inflammatory response into skin and joints. Besides no side effects was observed during etanercept administration. This study indicates that anti-TNF-α therapy might be used to treat immune-mediated inflammation likely to PsA in pediatric patients.  

Torsten Willenberg
Gefässzentrum Bern, VASC AI, Lindenhofspital Bern, Switzerland

Simon Bossart
Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Switzerland

Abstract

The mode of treatment of varicose veins has changed substantially over the last 20 years. Minimal invasive techniques have been established and seek the most gentle and safest way of treatment. Ultrasound is the basic instrument to guide these techniques. Endothermal ablation with laser or radiofrequency has become the standard technique for treatment of axial reflux. It requires local tumescence anaesthesia. Other, tumescencless techniques have been developed and established. Today there are many minimal invasive ways to treat varicosity. The treatment strategy can be tailored to the individual patient.

Thanet Pongcharoensuk
Phramongkutklao hospital

Chutika Srisuttiyakorn
Phramongkutklao hospital

Abstract

Erythroderma is a medical condition characterized by inflammation involving skin over 90% of the body’s surface area. This condition can result in high mortality rate and many systemic complications including fluid and electrolyte imbalance, infections, thermoregulatory disturbance and high output cardiac failure. In Thailand, limited data have been reported in the literature.

This study aims to investigate epidemiologic, clinical and histologic data relevant to etiologies of erythroderma among adults.

We performed a retrospective study among all patients acquiring erythroderma, aged above 16 years and visiting at the Division of Dermatology, Department of Internal Medicine, Phramongkutklao Hospital, Thailand from January 2015 to December 2019. The following data were recorded: personal data, medical history, clinical manifestations, histopathologic results, possible etiologies, laboratory profiles, treatment methods and outcomes.

During the 5-year study, 35 patients with erythroderma were collected. Men outnumbered women 6:1 (30 men and 5 women). The age of these patients ranged from 18-90 with mean age of 66.4 years. Idiopathic was the predominant etiology with 20/35 cases (57.1%), followed by drug eruption (17.1%). Herbal medicine (33.3%) and spironolactone (33.3%) were the most implicated drugs. Pre-existing skin diseases were observed including psoriasis (17.1%), pityriasis rubra pilaris (2.8%) and malignancy associated erythroderma (2.8%). Epidermal spongiosis was the most common histological feature observed in all etiologies (85.7%), (p=0.029). Complete clearance was obtained in 15/35 (42.8%). Death 2/35 (5.6%) occurred in one patient with drug reaction and one patient with pemphigus vulgaris associated erythroderma complicated with sepsis.

Although data are limited, erythroderma remains a serious condition effecting quality of life of patients. Our study demonstrated further epidemiology, etiologies and clinicopathologic information of erythroderma among Thai patients.

Anna Korsgaard Berg
Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark

Claus Zachariae
Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Gentofte, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Kirsten Nørgaard
Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark ; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Jannet Svensson
Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark;  Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.; University of Linköping, Sweden; Department of Pediatrics, Herlev and Gentofte Hospital, Herlev, Denmark

Abstract

Diabetes devices, such as insulin pumps, glucose sensors, and integrated automated insulin delivery systems, have brought about a transformative impact on the management of diabetes. This impact has been particularly significant for individuals with type 1 diabetes and increasingly for those with type 2 diabetes. These devices are designed for continuous wear, necessitating the consistent use of infusion sets, patch pumps, or glucose sensors that are inserted into the skin.

Regrettably, numerous studies have highlighted that skin-related issues stemming from diabetes devices are rather common. These problems encompass various forms of skin injury, allergic and irritative contact dermatitis, itching, wound formation, scarring, and lipodystrophies. The utilization of diabetes devices, both in the present and the foreseeable future, faces significant challenges due to these skin complications, but preventive strategies exist for especially skin injuries including use of a skin care regimen or patches. These challenges culminate not only in the discontinuation of device usage but also in decrease in quality of life and heavier disease burden.

This narrative literature review comprehensively synthesizes existing knowledge about skin problems triggered by diabetes devices, encompassing children, adolescents, and adults. The review delves into definitions, underlying causes, prevention strategies, and treatment approaches. Finally, the review provides recommendations for future research directions in skin problems and suggestions for advancement of in the part of diabetes devices in close contact with the skin to reduce device-related skin problems.

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