Ocorrência de carcinoma espinocelular labial não melanocítico em usuários crônicos de hidroclorotiazida / Occurrence of non-melanoma labial squamous cell carcinoma in chronic users of hydrochlorothiazide

Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)

Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)

What is the relationship between photosensitizing drugs and skin cancer?

ABSTRACT: Many medications are associated with phototoxicity or photoallergy, the two types of photosensitivity. Recently, a warning related to increased skin cancer risk was added to the labeling of the popular diuretic hydrochlorothiazide. This article reviews some photosensitizing medications and describes patient education on preventing and recognizing photosensitivity reactions and skin cancer.

[Current problems of polypharmacy in geriatric patients when taking drugs with a risk of photosensitivity.]

The article presents an overview of the current problems of polypharmacy in geriatric patients when taking drugs with a risk of photosensitivity. The article contains information about emerging adverse drug reactions, as well as methods for diagnosing, correcting and preventing phototoxic and photoallergic reactions in patients of older age groups. The main aspects of dermatological support in the system of long-term care for geriatric patients when taking drugs with a risk of photosensitivity are outlined. Clinical signs of senile xerosis and skin manifestations of adverse drug reactions were studied when taking drugs with the risk of photosensitization before and after the use of a photoprotector in elderly patients.

Efficacy Of Methotrexate Versus Azathioprine In The Treatment Of Chronic Actinic Dermatitis: A Randomized Control Trial.

Background: Azathioprine is first line immunosuppressive agent in treatment of chronic actinic dermatitis. The role of methotrexate has been effective in different dermatosis and it seems reasonable to use it in the treatment of chronic actinic dermatitis. Aims: We sought to compare the efficacy of methotrexate versus azathioprine in treatment of chronic actinic dermatitis. Methods: Patients with chronic actinic dermatitis were randomized to receive methotrexate in group A and azathioprine in group B. The response to treatment in terms of percentage PASI reduction and side effects of medications were assessed 12 weeks follow-up. Results: In group A, the percentage PASI reduction was <25% in 2 (1.19%) patients, 25-49% in 47 (27.9%) patients, 50-74% was achieved by 35 (20.8%) patients while in group B, the percentage PASI reduction of 25% was achieved by 2 (1.19%) patients, 25-49% in 45 (26.7%) patients, 50-74% in 37 (22.0%) patients. More than or equal to 75 percentage PASI reduction was not achieved by any patient in the study. Both drugs were found efficacious in treatment of CAD. A total of 23 (27.38%) patients in group A and 22 (26.19%) patients in group B showed derangement in laboratory investigations during 12 weeks treatment. The limitation of study was inability to do photo-patch test, so patients were diagnosed clinically and biopsy was done in clinically challenging cases. Conclusion: : This study shows that methotrexate is equally effective as azathioprine in the treatment of chronic actinic dermatitis with its added benefits of being cost effective and better safety profile.

Insights into proton pump inhibitor-induced photosensitivity: An observational study in a tertiary photobiology service.

BACKGROUND: Proton pump inhibitors (PPIs) are extensively prescribed but may cause photosensitivity and drug-induced lupus erythematosus (DILE), which can be overlooked as the drug may have been taken for years prior to presentation. METHODS: We reviewed the clinical and investigation findings of patients diagnosed with PPI-induced photosensitivity, diagnosed through the Scottish Photobiology Service. RESULTS: We report 11 patients with median age of onset 61-years and mean duration of PPI ingestion of 5-years [DILE (n = 6), phototoxicity (n = 3) and drug-induced solar urticaria through a lupus mechanism (n = 2)]. Five had Anti-Ro antibodies (three also ANA positive). Predominantly UVA and visible light photosensitivity was observed on phototesting. DISCUSSION: PPIs are a reversible cause of photosensitivity and DILE. Time to onset from drug initiation to symptoms can be prolonged, so clinicians should have a high index of suspicion in those taking PPIs. Most are diagnosed through clinical assessment and lupus serology, with phototesting indicated if there is diagnostic uncertainty.

Photodermatitis and ocular changes in nine horses after ingestion of wild parsnip (pastinaca sativa).

BACKGROUND: Primary photosensitization rarely occurs in horses and can easily be misinterpreted. Descriptions of the disease in horses after ingestion of parsnip are lacking. The aim of this case series was to describe the dermatological and ocular changes due to photosensitization and to raise awareness of parsnip being a possible aetiologic agent. CASE PRESENTATION: Nine horses from three different stables in Berlin and Brandenburg, Germany, presented variable degrees of erythema, scaling, crusting and necrosis of unpigmented skin at the head and prepuce. Horses were of different breeds with a median age of 15 ± 5.9 years. A mild leukocytosis was diagnosed in 1/9 horses at admission. Analyzed liver enzymes were within the reference ranges in all horses. Ocular changes were diagnosed as follows: blepharitis (3/9), conjunctivitis (7/9), corneal edema without additional signs of keratitis and/or uveitis (2/9), corneal edema with signs of uveitis (1/9) and photophobia (4/9). One horse developed a fluorescein positive corneal erosion. Skin biopsy (1/9) revealed a moderate to severe acute, eosinophilic and lymphocytic dermatitis with dermal edema and vasculitis. All stables housing these patients fed hay from the same distributer. Analyzed hay samples showed high contents of wild parsnip (plants, seeds, roots). Wild parsnip is widespread in Europe and contains furocoumarins, a family of photodynamic pigments, which may cause primary photodermatitis, keratoconjunctivitis and uveitis. Horses were treated according to severity of clinical symptoms systemically with flunixine meglumine (1.1 mg/kg BW 1-2x/day) or prednisolone (1 mg/kg BW 1x/day). Topically, either gentamicin (3x/day), dexamethasone (2-3x/day) and/or atropine (1x/day) were used. Skin care was provided with almond oil or dexpanthenol (2x/day). All horses were kept in a dark environment or were treated with sunscreen and facemasks. Duration of treatment varied from 6-30 days (median 11.3 days). CONCLUSION: Ingestion of wild parsnip (Pastinaca sativa) can induce primary photosensitization with dermatitis and ocular injury in horses. In times of extreme weather, hay may alter in botanical composition, resulting in high amounts of uncharacteristic plants causing novel problems.

Photosensitizing drug reactions.

Photosensitizing drug reactions are cutaneous eruptions that occur after exposure to ultraviolet radiation in patients using photosensitizing medications. The reactions can be broadly classified into phototoxic and photoallergic, with the former being much more common and well documented. There is an extensive list of photosensitizing medications, especially in the case of phototoxicity. The most common are amiodarone, chlorpromazine, doxycycline, hydrochlorothiazide, nalidixic acid, naproxen, piroxicam, tetracycline, thioridazine, vemurafenib, and voriconazole. Most of the medications implicated in photosensitivity share an action spectrum within the ultraviolet A range. Distinguishing between phototoxicity and photoallergy can be difficult, because some clinical overlap exists between the two disorders. It is often done based on pathogenesis, clinical presentation, and diagnosis. Management is similar for both types of reactions, with the gold standard being prevention. This review provides an overview of the photosensitizing drug reactions and highlights the similarities and differences between phototoxicity and photoallergy, as well as other photosensitizing drug reactions in the phototoxicity family including lichenoid reactions and pseudoporphyria.

Tricyclic antidepressant-induced photosensitivity; A case report and systematic review.

BACKGROUND/PURPOSE: Tricyclic antidepressants (TCAs) are still widely used and are available to purchase without prescription in some countries. Awareness of adverse cutaneous drug reactions is essential. METHOD: We reported a case of photo-distributed hyperpigmentation due to imipramine and carried out a systematic search of the related articles using the search terms "tricyclic antidepressants" or "tricyclic antidepressive agents", and "hyperpigmentation" or "photosensitivity disorder". Fifty non-duplicate citations were identified of which 28 articles which were independently assessed in full. The review was registered in PROSPERO, CRD42018107338. RESULTS: The remaining 25 articles met our inclusion criteria. Photo-distributed hyperpigmentation tricyclic antidepressant-induced photosensitivity reactions (TIPs) was the most common presentation. In 21 cases, this presented as an asymptomatic discolouration of exposed sites. Imipramine (81%), amitriptyline (9.5%), desipramine hydrochloride (4.8%) and mirtazapine (4.8%) were reported to be the culprit drugs. Nineteen were female with a mean age at presentation of 55 years. Mean duration from commencing the culprit drug until the development of discolouration was 10.4 years. Mean daily dose was 222.7 mg for imipramine. Histology was characteristic with golden-brown or brownish granules deposited in dermis. Staining for Masson-Fontana and MEL-5 was positive in all cases. Phototesting had not been done in cases prior to ours (negative 3 months after discontinuation of imipramine). Three further reports of suspected TIP presented with non-specific and eczematous eruption. The two presentations were reported along with systemic problems (thrombocytopenia and hepatic injury). CONCLUSIONS: This systematic review highlights the characteristic features of exposed site hyperpigmentation of TCA-induced photosensitivity occurring after prolonged drug exposure in many cases.

Retrospective analysis of skin photosensitivity induced by pirfenidone.

WHAT IS KNOWN AND OBJECTIVE: Knowledge regarding the association between photosensitivity and pirfenidone is based mainly on case reports. The purpose of this article was to evaluate the clinical characteristics of photosensitivity associated with pirfenidone. METHODS: We collected studies on photosensitivity induced by pirfenidone published from 2008 to 31 August 2021 in Chinese and English for a retrospective analysis. RESULTS AND DISCUSSION: The median age was 70 years (range 57-80) in 22 patients with pirfenidone-induced photosensitivity. The dose at the onset of symptoms ranged from 600 to 2403 mg for the treatment of idiopathic pulmonary fibrosis. Pirfenidone-induced photosensitivity occurred within 1 week in some patients and up to 8 months in others. The most common clinical manifestation of photosensitivity caused by pirfenidone was itching on body parts exposed to sunlight (back of hands, face, neck, and limbs) in 15 patients followed by erythema in 13 patients. Histopathological examination revealed necrotic keratinocytes, lymphocytic inflammatory cell infiltrate, hyperkeratosis and liquefaction degeneration in 5 patients. The photosensitivity test showed a markedly decreased minimum erythema dose (MED) of 7-228 mJ/cm2 UV-B in 4 patients and 4.86-12 J/cm2 UV-A in 5 patients. The clinical symptoms were significantly improved or completely relieved with a median time of 4 weeks (range 1-8) after drug withdrawal, dose reduction or systemic and topical glucocorticoid therapy. WHAT IS NEW AND CONCLUSION: Clinicians should be aware of the potential phototoxic effects of pirfenidone and should inform patients to take pirfenidone during (or after) a meal, avoid sun exposure, wear protective clothing, and apply broad-spectrum sunscreen with high ultraviolet UVA and UVB protection.

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study.

BACKGROUND: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. METHODS: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. RESULTS: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use. CONCLUSIONS: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. IMPACT: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.

Benzodiazepine-induced photosensitivity reactions: A compilation of cases from literature review with Naranjo causality assessment.

OBJECTIVE: Benzodiazepines have been reported to cause photosensitivity reactions. We characterized the clinical presentation and diagnosis of benzodiazepine-associated photosensitivity and adjudicated these cases for a causal association with benzodiazepines. METHODS: A literature search on PubMed's "MeSH" search feature and CINAHL (1964 to 2019) was performed using search terms: benzodiazepine, photosensitivity, and photosensitivity disorders/chemically induced. We applied the Naranjo scale, a standardized causality assessment algorithm, to identified cases. RESULTS: We identified eight published cases, with 50% of patients being female with a mean age of 46.3 years. Alprazolam, tetrazepam, clobazam, and clorazepate induced phototoxic reactions. Chlordiazepoxide induced one photoallergic reaction. Photosensitivity occurred between 1-3 days (37.5%), 7-14 days (25%), and >14 days (25%). Photosensitivity resolved after drug discontinuation within 2 weeks (62.5%). Benzodiazepine rechallenge confirmed photosensitivity in 75% of cases. Photopatch testing was negative in two patients; however, these patients had positive oral provocation testing. However, an oral photoprovocation test, an ideal diagnostic test, was not administered to several patients. Despite these challenges, the Naranjo scale identified 5 cases as definite benzodiazepine-induced photosensitivity. CONCLUSION: Five benzodiazepines induced photosensitivity reactions. Five patients showed a definite association with the Naranjo scale. Reporting to pharmacovigilance databases may help identify other benzodiazepines causing photosensitivity reactions.