Xeroderma Pigmentosum: Part Two: Treatment of Skin Tumors with Topical Podophyllin 25% in Benzoin.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease; relatively mild XP patients are sometimes designated as having pigmented xerodermoid or xerodermoid pigmentosum (XP-V), a variant of XP. It is commonly associated with many long-standing skin conditions and tumors, including malignancies, management of which is necessary to prevent the progress of the disease. The objective of the study was to evaluate an innovative therapeutic treatment, beyond surgery, surgical excision, cryotherapy, electrocautery and curettage, or Mohs surgery, for the management of skin tumors in XP.This was a prospective therapeutic interventional study comprising 50 patients with XP-V. Age of subjects ranged from 2 to 50 years, with a mean age of 18 years. Several measures were evaluated in part one of this study, and a number of others (as reviewed in part one) were successful in prophylaxis of skin tumors in XP as well as in treating earlier stigmata of XP; however, these measures were notably less successful in treating well-developed skin tumors in XP patients, and 18 of the 50 patients evaluated in part one had well-developed tumors (total 22 lesions) refractory to treatments. Podophyllin 25% in 100-mL tincture of benzoin was applied topically to lesions until complete resolution was documented in 18 patients with XP complications, such as keratoacanthoma (KA), basal cell carcinoma, or squamous cell carcinoma. Topical podophyllin 25% in benzoin was a less destructive alternative treatment for skin cancer and KA in XP patients.

The therapeutic dental challenge of xeroderma pigmentosum patients: case report.

Xeroderma pigmentosum (XP) is a rare genetic disease characterized by a hypersensitivity to ultraviolet (UV) radiation leading to defective deoxyribonucleic acid (DNA) repair and predisposing to skin tumorigenesis. This paper reports the safe approaches used for the dental treatment of XP patients, controlling the ultraviolet (UV) sources at the dental office. An XP 29-year-old woman was referred for oral pain and sensitivity at the service of periodontology, UV rays were checked with a UV-meter. During the examination, the patient kept her sunglasses while the practitioner was dressed in dark colors using an anti-UV filter over the surgical light. Facial dark brown pigmentations, limited mouth opening, tumor resection scar on the tongue, moderate periodontitis, and dental caries were noticed. Moderate periodontitis and dental caries were diagnosed. Treatment was planned in collaboration with the dermatologist. Soft scaling and root planning were performed in short sessions and self-curing material was used for coronary fillings after caries removal. In taking care of XP patients, particular attention should be given by dental professionals to: i) the office management for a UV-safe environment; ii) the adoption of suitable dental care and safe biomaterials with short sessions and regular controls; and iii) the adoption of personal protections by patients and practitioners.

Deep intronic founder mutations identified in the ERCC4/XPF gene are potential therapeutic targets for a high-frequency form of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a genodermatosis defined by cutaneous photosensitivity with an increased risk of skin tumors because of DNA repair deficiency. The worldwide prevalence of XP is ~1 to 4 in million, with higher incidence in some countries and regions including Japan (1 in 22,000) and North Africa due to founder mutations and a high degree of consanguinity. Among XP, the complementation group F (XP-F), is a rare form (1% of worldwide XP); however, this is underdiagnosed, because the ERCC4/XPF gene is essential for fetal development and most of previously reported ERCC4/XPF pathogenic variants are hypomorphs causing relatively mild phenotypes. From the largest Japanese XP cohort study, we report 17 XP-F cases bearing two pathogenic variants, both identified in deep intronic regions of the ERCC4/XPF gene. The first variant, located in intron 1, is a Japanese founder mutation, which additionally accounts for ~10% of the entire Japanese XP cases (MAF = 0.00196), causing an aberrant pre-mRNA splicing due to a miss-binding of U1snRNA. The second mutation located in intron eight induces an alternative polyadenylation. Both mutations cause a reduction of the ERCC4/XPF gene expression, resulting in XP clinical manifestations. Most cases developed early-onset skin cancers, indicating that these variants need critical attention. We further demonstrate that antisense oligonucleotides designed for the mutations can restore the XPF protein expression and DNA repair capacity in the patients' cells. Collectively, these pathogenic variants can be potential therapeutic targets for XP.

Xeroderma pigmentosum: case report.

OBJECTIVE: The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early diagnosis in patients with xeroderma pigmentosum (XP). CASE DESCRIPTION: An 8-year-old male patient was referred to the Joana de Gusmão Hospital (HIJG) in 2021 for evaluation and specialized care. Previously, the child was followed in his place of origin by oncologic and palliative care, where he was submitted to surgeries and chemotherapy. He was admitted to the HIJG using vismodegib, acitrein, tramadol, and solar protective measures. On physical examination, there were tumors and disseminated macular verrucous and ulcerated lesions. The imaging examination showed solid and expansive lesions on the face, and atelectasis and fibroscarring changes in the lung. The histopathological report proved the existence of melanocanthoma, carcinoma, and pyogenic granuloma. After the evaluation of the case, no surgery, chemotherapy, or radiotherapy was performed. It was decided to maintain the palliative treatment and to continue the use of tramadol for pain, and vismodegib and acitretin were used to control carcinomas and prophylactic measures. COMMENTS: The XP is a rare disease of autosomal recessive inheritance whose mechanism comes from failure in the DNA repair by exposure to ultraviolet rays, resulting in lesions on the skin and mucous membranes. They start as sunburns and can progress to melanosis, areas with altered pigmentation, premature aging, poikiloderma, and areas of high risk for neoplasms.

Therapeutics of xeroderma pigmentosum: A PRISMA-compliant systematic review.

Xeroderma pigmentosum is a rare hereditary autosomal recessive genodermatosis. At present, there are many treatment options for xeroderma pigmentosum, covering medical/procedural, surgical and combined modalities. However, the quality of these interventions has not been assessed. Our study aimed to perform a systematic review of the literature regarding the treatment of xeroderma pigmentosum. Multiple medical databases were accessed with the Medical Subject Headings terms; "xeroderma pigmentosum," "therapeutics" and "surgical procedures, operative" from January 2000 to April 2019, including articles published in Portuguese, Spanish and English (PROSPERO-CRD42018114858). Two hundred and ninety-eight studies were found in the databases researched, of which, after applying the inclusion criteria, only 33 studies remained. The 33 complete articles were read by three of the authors, having been found: 16 reported medical/procedural and 17 reported surgical treatments. Only one clinical study presented a good level of evidence (EL: 2): a randomized clinical trial using a T4 endonuclease V (T4N5) liposome lotion which reduced the development of skin lesions in patients with xeroderma pigmentosum. Amongst surgical modalities, all studies presented low evidence level (EL: 4). Three illustrative cases are also presented, to emphasize the multiple number of times that surgical modalities may be required in these patients. The therapeutic modalities, both clinical and surgical, for xeroderma pigmentosum presented a low level of scientific evidence which did not allow meta-analysis. More therapeutic studies, both clinical and surgical, with better scientific evidence are needed.

Conjunctival melanoma in patients with xeroderma pigmentosum: a series of four cases.

PURPOSE: To study the demographic features, treatment, histopathology, and outcomes in patients of xeroderma pigmentosum (XP) with conjunctival melanoma. METHODS: Retrospective case series. RESULTS: The median age at presentation was 18 years (range 9-30 years). There were three females and one male patient presenting with a median duration of symptoms of 3 months (range 1-60 months). The tumor was located in the bulbar conjunctiva in all 4 patients. All patients had corneal involvement by the tumor. The median tumor basal diameter was 7 mm (range 4-15 mm). Wide tumor excisional biopsy with alcohol keratoepithelectomy, cryotherapy to the free margins, and amniotic membrane grafting was done in three patients. One patient underwent orbital exenteration for extensive tumor. One patient also received adjuvant plaque brachytherapy for microscopic residual tumor. Over a median follow-up of 22 months (range 2-101 months), there were no recurrences, metastasis, or death. CONCLUSION: Conjunctival melanoma in XP is rare and manifests at a younger age.

Forms, interactions, and responses to social support: A qualitative study of support and adherence to photoprotection amongst patients with Xeroderma Pigmentosum.

OBJECTIVES: Social support influences adherence to treatment in chronic illness, but there is uncertainty about its facilitators and constraints. This study explored the forms, processes, and responses associated with mobilization of informal support across three life contexts amongst patients with Xeroderma Pigmentosum (XP), a condition requiring rigorous photoprotection to reduce cancer risks. DESIGN: Qualitative interview study. METHODS: A total of 25 adults with XP participated in semi-structured interviews conducted face to face. An inductive thematic analysis was applied using a framework approach. RESULTS: Practical support, involving both assistance with recommended photoprotection and adjusting daily activities to reduce exposure, was the key form of support provided by family and friends. However, responses to this support differed with two groups identified based on the relative priority given to photoprotection in daily life and processes of disclosure. For 'positive responders', support aligned with their own priorities to photoprotect, conveyed feelings of being cared-for and was facilitated by talking openly. In contrast, for 'negative responders' support conflicted with their priority of living 'normally' and their limited disclosure hindered receipt of helpful support in personal, clinic, and work interactions. Fears of workplace stigma also reduced disclosure amongst participants open in other contexts. CONCLUSIONS: Practical support conveyed psychosocial support with positive effects on adherence. This suggests the traditional separation into practical and emotional support is overly simplistic, with measures potentially missing important aspects. Interactional processes contribute to the effects of support, which can be addressed by targeting disclosure, stigma, and other barriers at individual and organizational levels. Statement of contribution What is already known on this subject? Social support can be both a facilitator and a hindrance to treatment adherence. Practical support is identified as the most important form of support in the context of adherence. The processes of support underpinning its relationship to adherence are unclear. What does this study add? Variations in the provision and impacts of support are influenced by participants' disclosure and attitudes to photoprotection, with two key groups comprising 'positive responders' and 'negative responders'. The influence of emotional support on adherence may be underestimated through neglect of the ways in which practical support often conveys feelings of being valued and cared-for. Barriers to mobilizing effective adherence support extends across life spheres, with fears of stigma and discrimination in work settings highlighting the need to intervene at individual and organizational levels.

Evaluation of a personalised adherence intervention to improve photoprotection in adults with Xeroderma Pigmentosum (XP): protocol for the trial of XPAND.

INTRODUCTION: Poor adherence to photoprotection for people with xeroderma pigmentosum (XP) can be life-threatening. A randomised controlled trial (RCT) is being conducted to test the efficacy of a personalised adherence intervention (XPAND) to reduce the level of ultraviolet radiation (UVR) reaching the face, by improving photoprotection activities in adults with XP. METHODS AND ANALYSIS: A two-armed parallel groups RCT, where we randomised 24 patients with suboptimal adherence to either an intervention group who received XPAND in 2018 or a delayed intervention group who will receive XPAND in 2019. XPAND involves seven sessions, one-to-one with a facilitator, using behaviour change techniques and specially designed materials to target barriers to photoprotection. Following baseline assessment in April 2018 (t0) and intervention, the primary outcome will be measured across 21 consecutive days in June and July 2018 (t1). The primary outcome is the average daily UVR dose to the face (D-to-F), calculated by combining objective UVR exposure at the wrist (measured by a dosimeter) with face photoprotection activities recorded on a daily UVR protection diary. Secondary outcomes include average daily UVR D-to-F across 21 days in August (t2); psychosocial process variables measured by daily questions (t0, t1, t2) and self-report questionnaires (t0, t1, t2, December 2018 (t3)). Intervention cost-utility is assessed by service use and personal cost questionnaires (t0, t3). The delayed intervention control arm participants will complete three further assessments in April 2019 (t4) and June-July 2019 (t5), and December 2019 (t6) with dosimetry and UVR protection diary completed for 21 days at t4 and t5. A process evaluation will be conducted using mixed methods. ETHICS AND DISSEMINATION: Ethical approval has been received from West London & GTAC REC 17/LO/2110. Results will be disseminated in peer-reviewed journals and at conferences. This study tests a novel intervention, which, if successful, will be integrated into routine care. TRIAL REGISTRATION NUMBER: NCT03445052; Pre-results.

Psychological correlates of adherence to photoprotection in a rare disease: International survey of people with Xeroderma Pigmentosum.

OBJECTIVES: Xeroderma pigmentosum (XP) is an extremely rare genetic disorder (approximately 100 known cases in the United Kingdom), where DNA damage caused by ultraviolet radiation in daylight cannot be repaired. Adherence to photoprotection is essential to prevent skin cancer. We investigated psychological correlates of photoprotection in the XP population of Western Europe and the United States. DESIGN: Cross-sectional survey of adults with XP and caregivers of patients <16 years and those with cognitive impairment in the United Kingdom, Germany, the United States, and France (n = 156). METHODS: Photoprotection activities to protect the face and body when outdoors; avoidance of going outside during daylight hours; intention; self-efficacy; and social support were assessed using measures developed for this study. Participants answered questions about their illness representations of XP (BIPQ); beliefs about photoprotection (BMQ); automaticity (i.e., without conscious effort) (SRBAI); clinical and demographic characteristics. Ordinal logistic regressions determined factors associated with photoprotection. RESULTS: One third did not achieve optimal face photoprotection. After controlling for demographic and clinical factors, modifiable correlates of higher photoprotection included greater perceived control of XP, stronger beliefs in necessity and effectiveness of photoprotection, and higher intention. Avoidance of going outside was associated with greater photoprotection concerns, more serious illness consequences, and higher XP-related distress. Greater automaticity and higher self-efficacy were associated with better protection across all outcomes. CONCLUSIONS: Approximately half of all known cases across three European countries participated. Identified modifiable predictors of photoprotection may be targeted by interventions to reduce the incidence of skin cancers in the immediate future, when a treatment breakthrough is unlikely. Statement of contribution What is already known on this subject? Adherence to photoprotection in other populations at elevated risk from skin cancer is poor; however, the level in XP is unknown. Research across chronic conditions shows that adherence to treatment and lifestyle recommendations are influenced by illness perceptions, self-efficacy, and treatment beliefs. Studies on photoprotection conducted with the general population have found that perceived risk, perceptions of ultraviolet radiation (UVR) protection, self-efficacy for the behaviour, and automaticity (behaviours that are enacted with little conscious awareness) are related to better photoprotection. What does this study add? This is the first international survey to examine adherence and its correlates in people with XP (an under-researched group at very high risk of fatal skin cancer). Adherence varies and at least one third have potential for improvement. Perceptions about XP, photoprotection beliefs, self-efficacy, intention, and automaticity were associated with photoprotection of the face and body when outdoors. Negative emotional representations of XP were associated with avoidance of going outside during daylight hours.

The influence of perceived medical risks and psychosocial concerns on photoprotection behaviours among adults with xeroderma pigmentosum: a qualitative interview study in the UK.

BACKGROUND: A high level of photoprotection is required by people with xeroderma pigmentosum (XP), a rare skin disease, to reduce skin cancer and other risks. However poor photoprotection is thought to be widespread. PURPOSE: This study examines the influences on photoprotection behaviours in adults with XP. DESIGN: Inductive qualitative study with semistructured interviews. Analysis employed a framework approach. SETTING: National sample recruited through a specialist XP centre in London. METHODS: Semistructured interviews at patients' homes. All transcripts were coded and themes charted for each participant. Comparisons within and across cases identified common themes and differing motivations and approaches to photoprotection. Credibility of interpretations assessed through patient/carer input and clinic adherence scores. PARTICIPANTS: 25 adults (17 male, eight female) aged 16-63 years with diagnosed XP attending a specialist centre. 18 lived outside London. RESULTS: Awareness of risks of ultraviolet radiation (UVR) and photoprotection was high. However, photoprotection behaviours varied according to perceived necessity and concerns. Three behavioural responses were identified: (1) 'dominated' by planning and routines to achieve a high level of photoprotection with significant activity restrictions and psychosocial impacts. (2) 'resistant' to photoprotection with priority given to avoiding an illness identity and enjoying a normal life. (3) Photoprotection' integrated' with an individual's life with little psychosocial impact. These responses were influenced by illness, personal and contextual factors including age, life stage and social support. Only the 'integrated' group achieved an equilibrium between perceived 'necessity' and 'concerns'. CONCLUSIONS: The personal balance between perceived risks of UVR and social/psychological 'concerns' led to differing behavioural responses and contributes to an understanding of adaptation and normalisation in chronic illness. The study will also inform a series of individualised behavioural interventions to reduce measured UVR exposure among people with XP that are potentially applicable to other conditions with high risks of skin cancer.

Ocular and Periocular Tumors in Xeroderma Pigmentosum: A Study of 120 Asian Indian Patients.

PURPOSE: We studied the incidence, treatment, and outcome of ocular and periocular tumors in patients with xeroderma pigmentosum (XP). DESIGN: Retrospective case series. METHODS: This single-institution study included 120 patients with XP who underwent intervention with excisional biopsy, enucleation, or orbital exenteration. The primary outcome measures were the occurrence of eyelid or ocular surface tumor, globe salvage, locoregional and systemic metastasis, and death. RESULTS: The mean age at presentation was 19 years. A family history of XP was present in 32 (27%) patients. Over a mean follow-up of 61 months, 34 (28%) patients developed no ocular/adnexal tumor, 86 (72%) developed ocular surface malignancy, 15 (13%) developed eyelid malignancy, and 22 (18%) developed other head and neck malignancies. Of the 86 patients with ocular surface malignancy, 48 (56%) had unilateral tumor and 38 (44%) had bilateral tumors. Invasive squamous cell carcinoma (n = 51, 41%) was the most common ocular surface tumor. Of the 15 patients with eyelid tumors, 14 (93%) had unilateral tumor and 1 (7%) had bilateral involvement. Basal cell carcinoma (n = 8, 50%) was the most common eyelid tumor. There were events of ocular surface tumor recurrence (n = 55 eyes, 44%), eyelid tumor recurrence (n = 5 eyes, 31%), locoregional lymph node metastasis (n = 3, 2%), systemic metastasis (n = 1, 1%), and death (n = 1, 1%). Overall, globe salvage was achieved in 119 (99%) patients (both eyes were salvaged in 92 [76%] patients and at least 1 eye was salvaged in 27 [23%] patients). CONCLUSION: XP is frequently associated with ocular surface, eyelid, and other head and neck malignancies. Lifelong follow-up is mandatory in these patients.

Novel therapeutic approaches to xeroderma pigmentosum.

BACKGROUND: The study of xeroderma pigmentosum has yielded unforeseen advances regarding how defects in the nucleotide excision repair pathway result in this devastating disease, but development of therapeutic strategies has trailed behind the mechanistic discoveries. OBJECTIVES: This review aims to cover clinical presentation, molecular mechanisms and current management, and highlights more recent insights into targeting the deficiencies secondary to the DNA repair defects to prevent skin cancer and/or neurological degeneration. METHODS: This review article discusses novel therapeutic approaches to xeroderma pigmentosum that focus on metabolic defects downstream of nucleotide excision repair. RESULTS: Current research demonstrates that specific sulfonylureas promote clearance of DNA damage and increase resistance to ultraviolet radiation in a cellular model of xeroderma pigmentosum. Moreover, nicotinamide attenuates the effects of ultraviolet radiation in cells, and caloric restriction decreases DNA damage burden in animal models of xeroderma pigmentosum. CONCLUSIONS: Clinical management of patients with xeroderma pigmentosum still focuses on preventative avoidance of sun exposure as opposed to therapies that would improve the patients' condition; thus, novel approaches to this disease are warranted.

Characteristics of Xeroderma Pigmentosum in Japan: Lessons From Two Clinical Surveys and Measures for Patient Care.

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by deficiency in repair of DNA lesions generated by ultraviolet radiation and other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun-exposed sites, and some patients show exaggerated severe sunburns even upon minimum sun exposure as well as neurological symptoms. We conducted a nationwide survey for XP since 1980. In Japan, the frequency of the XP complementation group A is the highest, followed by the variant type; while in the Western countries, those of groups C or D are the highest. Regarding skin cancers in XP, basal cell carcinoma was the most frequent cancer that afflicted patients with XP, followed by squamous cell carcinoma, and malignant melanoma. The frequency of these skin cancers in patients with XP has decreased in these 20 years, and the age of onset of developing skin cancers is higher than those previously observed, owing to early diagnosis and education to patients and care takers on strict prevention from sunlight for patients with XP. On the other hand, the effective therapy for neurological XP has not been established yet, and this needs to be done urgently.

Xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological involvement. This disease is related to a defect in genes within the nucleotide excision repair system for the first seven genetic groups (A-G), and to an abnormality in transcription groups for the eighth group (xeroderma pigmentosum variant - XPV). Cutaneous carcinomas are the most common types of cancer seen. They may begin in childhood. Multiple melanoma commonly occurs during the course of XP but given the frequency of spontaneous regression, the incidence is underestimated. The clinical appearance is characterised by polymorphous lesions with characteristic dyschromia and in most cases it is sufficient to establish the diagnosis. Investigation of unscheduled DNA synthesis (UDS) and cell survival following ultraviolet (UV) radiation were formerly considered the reference examination for laboratory diagnosis. However, these tests are now being replaced by new molecular biology techniques to screen for the genetic mutations characteristic of the disease. These techniques have proved extremely useful in identifying heterozygous patients and in antenatal diagnosis. Photoprotection is the key preventive measure: patients must avoid all exposure to the sun and to artificial sources of UV radiation. The therapeutic arsenal has recently been enriched by several modern therapeutic methods used to destroy cutaneous tumours such as imiquimod and photodynamic therapy (PDT). These approaches are valuable since they eliminate incipient tumours while sparing healthy skin. Surgery and cryosurgery are the most suitable methods for treating cutaneous tumours in children. Chemotherapy may be considered an alternative for the treatment of keratoacanthomas and squamous cell carcinomas (SCC). Cryosurgery may be combined with other therapeutic approaches to eliminate SCC of the lip. Management of these patients in reference centres, coupled with assistance from associations providing support for patients' families, has resulted in improved quality of therapy while slowing down disease progression.

Understanding and predicting a complex behavior using n-of-1 methods: Photoprotection in xeroderma pigmentosum.

OBJECTIVE: Xeroderma pigmentosum (XP) is a very rare inherited disease; the most important aspect of clinical management is rigorous photoprotection from ultraviolet radiation. The aims of this novel study were to (a) understand and categorize the behavioral complexity and within-participant variability in photoprotection of the face in XP; (b) determine the predictors of photoprotection; and (c) identify individual needs for personalized interventions. METHOD: A total of 20 adults with XP completed an ecological momentary assessment (EMA) study over 50 days. Measures included an ultraviolet radiation diary of photoprotective behaviors used at each outdoor occasion (e.g., hat, face visor, sunscreen), and a mobile phone survey assessing self-reported protection (0-100), satisfaction with protection achieved, and predictive variables (e.g., motivation, effort, mood). Descriptive statistics for photoprotective behavior were computed, per person. When possible, individual dynamic logistic regression models were used to investigate the predictors of photoprotection, and correspondence between self-reported protection and behavior. RESULTS: Photoprotection (clothing and sunscreen) was suboptimal for most participants, and discrepancies between self-reported protection and behavior were identified. Modeling of photoprotection was conducted for six participants who went outside sufficient times and used varied protection. Different predictors were identified across participants. Weekend versus weekday, physical symptoms, stress, and feeling self-conscious were most frequently associated with protection. CONCLUSION: The findings support the need for intervention and have implications for the selection of individually tailored behavioral outcomes and intervention targets to improve photoprotection. The method of profiling multiple preventive behaviors using EMA may be of use in other rare conditions involving complex behaviors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Xeroderma pigmentosum clinical practice guidelines.

Xeroderma pigmentosum (XP) is a genetic photosensitive disorder in which patients are highly susceptibe to skin cancers on the sun-exposed body sites. In Japan, more than half of patients (30% worldwide) with XP show complications of idiopathic progressive, intractable neurological symptoms with poor prognoses. Therefore, this disease does not merely present with dermatological symptoms, such as photosensitivity, pigmentary change and skin cancers, but is "an intractable neurological and dermatological disease". For this reason, in March 2007, the Japanese Ministry of Health, Labor and Welfare added XP to the neurocutaneous syndromes that are subject to government research initiatives for overcoming intractable diseases. XP is one of the extremely serious photosensitive disorders in which patients easily develop multiple skin cancers if they are not completely protected from ultraviolet radiation. XP patients thus need to be strictly shielded from sunlight throughout their lives, and they often experience idiopathic neurodegenerative complications that markedly reduce the quality of life for both the patients and their families. Hospitals in Japan often see cases of XP as severely photosensitive in children, and as advanced pigmentary disorders of the sun-exposed area with multiple skin cancers in adults (aged in their 20-40s), making XP an important disease to differentiate in everyday clinical practice. It was thus decided that there was a strong need for clinical practice guidelines dedicated to XP. This process led to the creation of new clinical practice guidelines for XP.

Xeroderma pigmentosum-Cockayne syndrome complex.

Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published information on XP-CS is mostly scattered throughout the literature. We compiled statistics related to symptom prevalence in XP-CS and have written a clinical description of the syndrome. We also drew on clinical practices used in XP and in Cockayne syndrome without XP to aid management of XP-CS.Extensive searches of the literature identified 43 XP-CS patients. The diagnosis had been confirmed with molecular or biochemical methods in 42 of them. Clinical features of each patient were summarized in spreadsheets and summary statistics were generated from this data. XP patients are classified into complementation groups according to the gene that is mutated. There are four groups in XP-CS, and classification was available for 42 patients. Twenty-one were in the XP-G complementation group, 13 in XP-D, 5 in XP-B, and 3 in XP-F. Overall, the clinical features of XP-CS are very similar to those of CS without XP, with the exception of skin cancers in XP-CS. However, one intriguing finding was that cancer incidence was lower in XP-CS compared to XP alone or XP-neurological disorder. The cancer rate in XP-CS was higher than in CS without XP, an unsurprising finding. There is preliminary evidence for the existence of severity groups in XP-CS, as is the case in CS.Although health problems in XP-CS vary both in severity and in when they the first occur, there was overall homogeneity between all complementation groups and putative severity groups. Severely affected patients met fewer milestones and died at younger ages compared to more mildly affected patients.