• Pemphigus vulgaris and bullous pemphigoid of the upper aerodigestive tract: a review article and novel approaches to management

      Hussain, Mohammed Hassan; Tanwir, Faiz; Sakagiannis, Georgios; Mair, Manish; Mahmood, Sara; Ashokkumar, Sithamparappillai (2021)
      Background: Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous pemphigoid. The oral cavity or oropharynx may be the initial site of presentation or often the only site involved. Summary: These conditions are often misdiagnosed or overlooked leading to poorer patient outcomes. Due to the chronic nature of these conditions and the systemic effects of treatment, there is a significant associated morbidity and mortality. As such, an understanding of the fundamentals of autoimmune bullous diseases is vital to those working in otolaryngology. The mainstay of management in both conditions is topical and systemic corticosteroids. There is also a role for immunomodulating and non-steroidal anti-inflammatory drugs as adjunct or alternative therapies. Surgical intervention may be required to protect the airway. Often multimodality treatment is required involving multidisciplinary input from otolaryngologists, oral surgeons, dermatologists, and rheumatologists. This review article will highlight the aetiology, pathology, clinical features, investigations, and management of both pemphigus vulgaris and bullous pemphigoid including recent advances in management.
    • Observational study to estimate the proportion of surgical site infection following excision of ulcerated skin tumours (OASIS study)

      Wernham, Aaron (2021-12-30)
      Background: Ulceration is a recognized risk factor for surgical site infection (SSI); however, the proportion of patients developing SSI after excision of an ulcerated skin cancer is unknown. Aim: To determine the proportion of participants with SSI after surgical excision of an ulcerated skin cancer. A secondary aim was to assess feasibility outcomes to inform the design of a randomized controlled trial to investigate the benefits and harms of perioperative antibiotics following excision of ulcerated tumours. Methods: This was a multicentre, prospective, observational study of patients undergoing excision of an ulcerated skin cancer between March 2019 and March 2020. Prior to surgical excision, surface swabs of the ulcerated tumours of participants recruited from one centre were undertaken to determine organism growth. At 4 weeks after surgery, all participants were e-mailed or posted the Wound Healing Questionnaire (WHQ) to determine whether they had developed SSI. Results: In total, 148 participants were recruited 105 (70.9%) males; mean ± SD age 77.1 ± 12.3 years. Primary outcome data were available for 116 (78.4%) participants, of whom 35 (30.2%) were identified as having an SSI using the WHQ with a cutoff score of 8, and 47 (40.5%) were identified with a cutoff score of 6. Using the modified WHQ in participants with wounds left to heal by secondary intention, 33 (28.4%) and 43 (37.1%) were identified to have SSI respectively. Conclusion: This prospective evaluation of SSI identified with the WHQ following excision of ulcerated skin cancers demonstrated a high proportion with SSI. The WHQ was acceptable to patients; however, further evaluation is required to ensure validity in assessing skin wounds.
    • Mutations in the ribosome biogenesis factor gene LTV1 are linked to LIPHAK syndrome, a novel poikiloderma-like disorder

      Helbling, Ingrid; Barwell, Julian (2022)
      In the framework of the UK 100000 Genomes Project, we investigated the genetic origin of a previously undescribed recessive dermatological condition, which we named LIPHAK (LTV1-associated Inflammatory Poikiloderma with Hair abnormalities and Acral Keratoses), in four affected individuals from two UK families of Pakistani and Indian origins, respectively. Our analysis showed that only one gene, LTV1, carried rare biallelic variants that were shared in all affected individuals, and specifically they bore the NM_032860.5:c.503A > G, p.(Asn168Ser) change, found homozygously in all of them. In addition, high-resolution homozygosity mapping revealed the presence of a small 652-kb stretch on chromosome 6, encompassing LTV1, that was common to and haploidentical in all affected individuals. The c.503A > G variant was predicted by in silico tools to affect the correct splicing of LTV1's exon 5. Minigene-driven splicing assays in HEK293T cells and in a skin sample from one of the patients confirmed that this variant was indeed responsible for the creation of a new donor splice site, resulting in aberrant splicing and in a premature termination codon in exon 6 of this gene. LTV1 encodes one of the ribosome biogenesis factors that promote the assembly of the small (40S) ribosomal subunit. In yeast, defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm; however, the role of this gene in human pathology is unknown to date. Our data suggest that LIPHAK could be a previously unrecognised ribosomopathy.
    • Impact of Diversity in Training Resources on Self-Confidence in Diagnosing Skin Conditions Across a Range of Skin Tones: An International Survey

      Roland, Damian (2022-02-25)
      Background: Medical images are invaluable in facilitating recognition of clinical signs. Recent studies highlight a lack of diversity of skin tone images used within medical education. However, there is a paucity of data on the impact of this on patient care. Aims: To investigate diversity in training resources used by users of an International online teaching platform and self-confidence in diagnosing skin conditions in all skin tones. Methods: Users of an online teaching platform (www.dftbskindeep.com) were invited to participate in a survey evaluating key points including geographical location, ethnicity, profession, specialty, years of experience, training resources and confidence in diagnosing skin conditions. Data analyses were performed using SPSS. Categorical variables were presented as proportions. Chi-squared or Fisher's exact tests were used to compare the distribution between groups as appropriate. Results: Of 600 participants, 74% reported training resources featuring predominantly white skin. Participants were "generally uncertain" in 43% cases, "sometimes uncertain but clinically safe" (52%), and "confident across a range of skin tones" in a minority (5%). Self-confidence was associated with location [higher in Africa (29%) and Latin America (11%), (p < 0.001)]; diversity of training resources [higher with a mix (10%) or darker tones (20%) (p < 0.001)]; clinical experience [6-10 (5%) or >10 years of practice (11%) (p < 0.001)] and specialty [highest in dermatologists (53%, p < 0.001)]. Self-confidence was lowest among pediatricians, emergency medicine and pediatric emergency medicine specialists (<5%). Conclusions: These data provide preliminary evidence that training resources used by healthcare professionals on a global scale may lack enough diversity on representation of skin images, and a lack of self-confidence in diagnosing pediatric skin conditions. Further work is needed to understand the impact on knowledge and patient care to ensure equitable healthcare for all.
    • Comparison of the prognostic value of microscopically measured invasive width versus macroscopic width in cutaneous melanoma shows the superiority of microscopic invasive width measurement

      Bamford, Mark; Udensi, Louisa; O'Riordan, Marie; Saldanha, Gerald (2022-03)
      Background: Invasive width, the distance between the most peripheral invasive melanoma cells on the section where Breslow thickness (BT) was measured, was recently identified as a prognostic feature. It is unclear whether a routine measurement is justified, given that macroscopic width is already included in many melanoma histopathology reports and may itself be a prognostic feature. This study sought to investigate this. Methods: A retrospective cohort of 718 melanoma patients in which macroscopic width had been stated in the original histopathology report was used. Survival analysis was performed. Results: Macroscopic and invasive widths were positively correlated (p < 0.001). Invasive width was typically smaller than the paired macroscopic width (median difference 3.7 mm, p < 0.001), a difference seen across all T groups. Both macroscopic and invasive widths were significantly associated with melanoma survival in Kaplan-Meier analysis, including overall survival, but invasive width survival curves were more widely separated. Both were significantly associated with outcome after correction for BT in Cox proportional hazards regression, but the models containing invasive width had a substantially better fit. Conclusions: This study shows that both macroscopic and invasive widths have prognostic values, but confirms that the latter is superior. It supports further investigation of this feature's prognostic value.
    • Translation into Spanish and Field-Testing of a New Score for Evaluating Psoriasis Severity: The Simplified Psoriasis Index (SPI)

      Helbling, Ingrid (2022-04)
      Background: The simplified psoriasis index (SPI) was developed in the United Kingdom to provide a simple summary measure for monitoring changes in psoriasis severity and associated psychosocial impact as well as for obtaining information about past disease behavior and treatment. Two complementary versions of the SPI allow for self-assessment by the patient or professional assessment by a doctor or nurse. Both versions have proven responsive to change, reliable, and interpretable, and to correlate well with assessment tools that are widely used in clinical trials - the Psoriasis Area and Severity Index and the Dermatology Quality of Life Index. The SPI has already been translated into several languages, including French, Brazilian Portuguese, Dutch, Arabic, and Thai. Objective: To translate the professional and self-assessment versions of the SPI to Spanish and to field test the translations. Method: A medically qualified native Spanish speaker translated both versions of the SPI into Spanish. The Spanish translations were discussed by comparing them to blinded back translations into English undertaken by native English speakers; the Spanish texts were then revised in an iterative process involving the translators, 4 dermatologists, and 20 patients. The patients scored their own experience of psoriasis with the self-assessment version and commented on it. The process involved checking the conceptual accuracy of the translation, language-related differences, and subtle gradations of meaning in a process involving all translators and a panel of both Spanish- and English-speaking dermatologists, including a coauthor of the SPI. Results: The final self-assessment and professional Spanish versions of the SPI are presented in this manuscript. Conclusions: Castilian Spanish translations of both versions of the SPI are now available for monitoring disease changes in Spanish-speaking patients with psoriasis under routine clinical care.
    • A review of Mohs micrographic surgery for skin cancer. Part 1: Melanoma and rare skin cancers

      Veitch, David; Wernham, Aaron (2022-05)
      Mohs micrographic surgery (MMS) is a precise and effective method commonly used to treat high-risk basal cell carcinoma and squamous cell carcinoma on the head and neck. Although the majority of evidence for MMS relates to keratinocyte cancers, there is published evidence for other types of skin cancer. This review aims to discuss the evidence for using MMS to treat six different types of skin cancer [malignant melanoma, lentigo maligna, dermatofibrosarcoma protuberans, atypical fibroxanthoma (AFX), microcystic adnexal carcinoma and pleomorphic dermal sarcoma (PDS)] particularly in the context of survival rates and cancer recurrence. These cancers were chosen because there was sufficient literature for inclusion and because MMS is most useful when cancers are contiguous, rather than for cancers with marked metastatic potential such as angiosarcoma or Merkel cell carcinoma. We searched MEDLINE, PubMed and Embase using the keywords: 'melanoma', 'mohs micrographic surgery', 'lentigo maligna', 'dermatofibrosarcoma protuberans', 'atypical fibroxanthoma', 'microcystic adnexal carcinoma' and 'pleomorphic dermal sarcoma' along with their appropriate synonyms, to identify the relevant English-language articles from 2000 onwards, given that literature for MMS on nonkeratinocyte cancers is sparse prior to this year. AMSTAR (A MeaSurement Tool to Assess systematic Review) was used to assess the validity of systematic reviews. Further high-quality, multicentre randomized trials are necessary to establish the indications and efficacy of MMS for rarer cancers, particularly for AFX and PDS, for which only limited studies were identified.
    • Use of perioperative prophylactic antibiotics following excision of ulcerated skin lesions in the UK: a national, multispeciality survey of clinicians

      Wernham, Aaron (2022-05)
      Skin cancer is the most common malignancy in the UK, and up to a third of lesions are ulcerated at the time of excision. Ulceration has been shown to increase the risk of developing surgical site infection following excision, with some studies finding infection rates of 33%. However, no specific guidelines for the use of antibiotic prophylaxis in such cases exist. We surveyed 129 clinicians (covering Dermatology, Plastic Surgery, Ear, Nose and Throat Surgery, and Oral and Maxillofacial Surgery) who all excise skin lesions on a regular basis. There was significant variability in their practice with regard to antibiotic prophylaxis, with 9% always prescribing them and 19% never prescribing them. Variation exists both among and between specialities. This variation increases the risk of antimicrobial resistance and shows a paucity of good clinical evidence, indicating that a well-designed clinical trial is needed to guide future practice.
    • Local anesthetics in dermatologic surgery: a review of adjuncts and pain reduction techniques

      Gnanappiragasam, Dushyanth; Veitch, David; Wernham, Aaron (2022-05-27)
      A variety of local anesthetic adjuncts exist for dermatological surgery. Similarly, many options to reduce the pain of local anesthesia exist. This review aims to summarise the evidence relating to local anesthetic adjuncts and methods to reduce the pain of local anesthesia. Adjuncts to local anesthetics can be an important consideration to optimise anesthetic effect. Current evidence suggests that buffering and warming local anesthetics, skin cooling, pinching, as well as administering vibrations to the skin are effective at reducing pain during administration. No significant difference was found between administering vibrations and skin cooling with regards to reducing pain. Studies demonstrate that overall, local anesthesia injection into distal sites is safe. However, there remains limited evidence specific to dermatologic surgery supporting ways to reduce pain during local anesthetic injection, and in determining the safety of local anesthetics for distal sites with confidence. Further high-quality research in the form of multi-centre randomised trials is required.
    • Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) Cohort: Feasibility data from a multi-centre prospective observational cohort study to inform a future Randomised Controlled Trial (RCT)

      Veitch, David (2022-06-03)
      Background: Compression therapy is considered beneficial for lower limb post-surgical wounds healing by secondary intention, however there is a lack of supportive evidence. To plan a randomised controlled trial suitable data is needed. Objectives: Determine feasibility of recruitment and estimate recruitment rate Understand the standard post-operative wound management pathway Determine uptake of optional additional clinic visit for healing confirmation Explore patient acceptability of compression bandaging and a future RCT METHODS: Participant recruitment over 22 months from secondary care Dermatology clinics. Eligibility criteria: INCLUSION: over 18 years; planned excision of keratinocyte cancer on lower leg with healing by secondary intention; ankle-brachial pressure index ≥ 0.8 EXCLUSION: planned primary closure/graft or flap; unable to receive/comply/tolerate high compression; planned compression; suspected melanoma Followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information collected on healthcare resource use, unplanned compression, wound healing, optional clinic visit to confirm healing. Results: 58 patients recruited from 9 secondary care dermatology clinics in 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n=53) attended weekly follow-up assessments. Standard care clinical contacts were: GP visits 7(1.2%), Community Nurse visits 169(28.5%), Practice nurse visits 189(31.8%), and Dermatology clinic visits 138(23.2%). Participants whose wounds healed, 34/45(75.6%) attended an optional clinic visit. Conclusions: Data were obtained to inform a future RCT. Recruitment rates are higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.
    • Toxic epidermal necrolysis-like lupus

      Roberts, Elizabeth; Melchionda, Veronica; Saldanha, Gerald; Shaffu, Shireen; Royle, Jeremy; Harman, Karen
      Toxic epidermal necrosis (TEN)-like lupus is a rare condition characterized by epidermal loss and mucosal ulceration occurring in patients with acute severe flares of systemic lupus erythematosus. The clinical picture may mimic drug-induced Stevens-Johnson syndrome/TEN; however, the absence of a suitable culprit drug, and the context of acute lupus point to the correct diagnosis. In a case series of three patients, further discriminating features included a slower onset of epidermal loss, more limited mucosal ulceration and a lack of ocular involvement when compared with drug-induced TEN. Histology may show similar features, including basal layer vacuolation, apoptosis and full-thickness epidermal necrosis. Patients with TEN-like lupus may have additional features of lupus, and a lupus band on direct immunofluorescence. It is important to identify this condition correctly, so that these patients can be appropriately managed with early input from Rheumatologists and prompt treatment with high-dose combined immunosuppressant therapy.
    • Dermatological surgery: an update on suture materials and techniques. Part 2

      Veitch, David; Wernham, Aaron
      This is the second part of a two-part series summarizing the latest evidence related to suture materials and wound closure techniques in dermatological surgery. We critically appraised evidence focusing on the following consequences of suture choice: scar/cosmesis, pain, patient satisfaction, cost, infection and wound complications. We searched the databases MEDLINE, PubMed and Embase using the keywords ‘skin surgery’, ‘dermatological surgery’, ‘sutures’, ‘braided sutures’, ‘monofilament sutures’ and ‘antibacterial sutures’ to identify relevant English-language articles. This part of the review assesses the evidence for different types of buried sutures, including braided vs. monofilament sutures, longer-absorbing sutures and antibacterial sutures. The majority of trials were noted to be of poor quality, single-centre (thus lacking external validity) and underpowered, which presents challenges in comparing suture techniques in skin surgery. Future large-scale, multicentre, randomized trials are needed, with both surgeon and patient-assessed validated outcomes.
    • Ideal proportion of the population to be patch tested: How many should we be doing?

      Johnston, Graham
      Background How many patients should we be patch testing? A previous study suggested that the minimum proportion of a population to be patch tested for allergic contact dermatitis was 1:700 annually. Objectives To evaluate if the current minimum rate for patch testing has changed over the 20 years since the previous study in order to maximize the value. Methods In cooperation with the British Society for Cutaneous Allergy, a proforma for collation of retrospective data between January 2015 and December 2017 was sent to patch-test centers in the United Kingdom (UK) and the Republic of Ireland (ROI). The number of positive tests was analyzed against the proportion of population tested to see what proportion of the population would yield the greatest number of positive results. Results Responses from 11 centers showed that the minimum number needed to patch test had increased to 1:550 per head of population per year using the current criteria. Conclusions In agreement with previous studies, we should be patch testing more people than we are. We could reduce the threshold for referral of patients we patch test to derive the most benefit from this investigation.
    • Dermatological surgery: an update on suture materials and techniques. Part 1

      Veitch, David; Wernham, Aaron
      Significant variation exists in the surgical suture materials and techniques used for dermatological surgery. Many wound-closure techniques are now practised, including use of sutures, staples and topical adhesives. The focus of our review article is to summarize the latest evidence relating to suture materials and wound-closure techniques, considering the following areas: scar/cosmesis, pain, patient satisfaction, cost, infection and wound complications. We searched the databases Medline, PubMed and Embase using the keywords 'skin surgery', 'dermatologic surgery', 'sutures', 'suture techniques', 'suturing techniques' and 'surgical techniques' to identify relevant English-language articles. Absorbable superficial sutures may be a preferred alternative to nonabsorbable sutures by both patients and surgeons. Subcuticular sutures may be preferable to simple interrupted sutures for superficial wound closure, and there may also be a role for skin staples in dermatological surgery, particularly on the scalp. However, there remains limited evidence specific to dermatological surgery supporting the use of particular suture materials and suturing techniques. Further high-quality research is required, including multicentre randomized trials with larger cohorts.
    • Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) Cohort Study: A multi-centre prospective observational cohort study in patients without planned compression

      Veitch, David
      Background: There is no agreed treatment pathway following excision of keratinocyte cancers. Compression therapy is considered beneficial for secondary intention healing on the lower limb, however there is a lack of supportive evidence. To plan a randomised controlled trial suitable data is needed. This paper reports a multi-centre prospective observational cohort study in this patient population, to inform a future trial design. Objectives: 1. To estimate the time to healing in wounds healing by secondary intention without planned post-operative compression, following excision of keratinocyte cancers on the lower leg 2. To characterise the patient population including factors affecting healing 3. To assess the incidence of complications METHODS: INCLUSION CRITERIA: People over 18 years; planned excision of keratinocyte cancer on lower leg with healing by secondary intention; ankle-brachial pressure index (ABPI) greater than or equal to 0.8; written informed consent EXCLUSION CRITERIA: Planned: primary closure, skin graft or flap; compression therapy for another indication; unable to receive, comply or tolerate high compression; planned compression; suspected diagnosis other than keratinocyte cancer. Results: This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n=53): mean age was 81 (range 25-97) years; median time to healing was 81(95% Confidence Interval:73-92) days and at 6-month 45 patients (84.9%) had healed. Healing prognostic factors were wound parameters, and ABPI. Wound infections occurred in 16 participants(30.2%) and 4(7.5%) were admitted to hospital. Conclusions: Data collected has informed the RCT preparation. A relatively high (7.5-15%) proportion of wounds not healed, incidence of infection and hospital admissions demonstrated the need for clearly establishing potentially effective treatments and improve outcomes for this population.
    • A multicentre qualitative study of patient skin surgery experience during the COVID-19 pandemic in the UK

      Gnanappiragasam, Dushyanth; Veitch, David; Wernham, Aaron
      Understanding patient concerns regarding skin surgery during the COVID-19 pandemic is a vital way of learning from individual experiences. A shift towards using superficial absorbable sutures (AS) has been anecdotally observed. We explored patient attitudes to the use of AS, and their experiences and perceptions of attending for skin surgery during the pandemic. In total, 35 participants were interviewed (74% men, 100% white British; mean age 72.5 years, range 43-95 years). Participants reported that they were reassured by precautions taken to minimize exposure and risk from COVID-19. The majority (86%) did not feel that personal protective equipment worn by staff impaired their experience, and 29% reported that their experience of attending for skin surgery during the lockdown period was more efficient and organized than on prepandemic visits. The vast majority (94%) of participants would opt to have AS again or had no strong preference for either suture type. Based on their experiences, most participants would have no concerns about attending for further skin surgery during the pandemic and would opt to have AS.