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We present a case with a phototoxic reaction following topical use of NSAID. The phototoxic reaction was initially mistaken for cellulitis which led to treatment with dicloxacillin, which led to an exanthematous drug eruption. The patient was treated with topical clobetasol propionate and oral non-sedating antihistamines. Follow-up revealed post-inflammatory hypopigmentation.
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The homeostasis of tissues in a chronic disease is an essential function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells with a consequent aggravation of symptoms. The protoporphyria (PP) is a rare chronic disease that causes phototoxicity in visible light with local skin pain and general malaise. In order to establish if there is a systemic involvement of the CS during sun exposure, we designed a non-invasive method with a serum collection in winter and summer from 19 PP and 13 controls to detect the levels of CS protein: Properdin, Factor H (FH), and C5. Moreover, the global radiation data were collected from the regional agency of environmental protection (ARPA). The results show growing values for every protein in patients with PP, compared to control, in both seasons, in particular in summer compared to winter. To reinforce the evidence, we have estimated the personal exposure of patients based on the global radiation data. The main factors of the AP increased over the season, confirming the involvement of the AP in relation to light exposure. The systemic response could justify the general malaise of patients after long light exposure and can be exploited to elucidate new therapeutic approaches.
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Vía Alternativa del Complemento/inmunología , Vía Alternativa del Complemento/efectos de la radiación , Proteínas del Sistema Complemento/inmunología , Susceptibilidad a Enfermedades , Protoporfiria Eritropoyética/etiología , Luz Solar/efectos adversos , Adulto , Biomarcadores , Complemento C5/inmunología , Complemento C5/metabolismo , Factor H de Complemento/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Properdina/inmunología , Properdina/metabolismo , Protoporfiria Eritropoyética/diagnóstico , Protoporfiria Eritropoyética/metabolismo , Estaciones del AñoRESUMEN
Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions represent one of the most common drug adverse events and are frequently an important issue to consider in the therapeutic management of patients. Phototoxicity and photoallergy are the two different pathogenic mechanisms involved in photosensitization. Related cutaneous manifestations are heterogeneous, depending on the culprit drug and subject susceptibility. Here we report an updated review of the literature with respect to pathogenic mechanisms of photosensitivity, clinical manifestations, patient management, and prediction and evaluation of drug-induced photosensitivity. We present and discuss principal groups of photosensitizing drugs (antimicrobials, nonsteroidal anti-inflammatory drugs, anti-hypertensives, anti-arrhythmics, cholesterol, and glycemia-lowering agents, psychotropic drugs, chemotherapeutics, etc.) and their main damage mechanisms according to recent evidence. The link between the drug and the cutaneous manifestation is not always clear; more investigations would be helpful to better predict drug photosensitizing potential, prevent and manage cutaneous adverse events and find the most appropriate alternative therapeutic strategy.
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BACKGROUND: Erythropoietic protoporphyria (EPP) is an ultra-rare genetic disorder (prevalence 1:150`000) characterized by instant painful phototoxic burn reactions in skin exposed to visible light. Afamelanotide is the first clinically tested therapy effectively increasing the time EPP patients can spend in direct sunlight without developing symptoms and reducing the number and severity of phototoxic reactions. OBJECTIVES: We report our data on real-world effectiveness of afamelanotide treatment in EPP and its phototoxic burn protection factor (PBPF). METHODS: We analysed clinical data collected between 2016 and 2018 in the Swiss EPP cohort (n = 39) on maximum phototoxic burn tolerance time (PBTT), i.e., maximum time spent in sunlight without phototoxic reaction, severity of phototoxic reactions as assessed by an 11-point Likert-type visual analogue scale (VAS), with 0 being no pain and 10 being the worst possible pain, and Quality of Life (QoL), as assessed with an EPP-specific instrument. RESULTS: Before treatment, the PBTT was median 10 min (IQR 5-20). Under treatment, PBTT increased to median 180 min (IQR 120-240). Individual PBPF increased 1.8- to 180-fold (full range, median 15). The pain severity of the worst phototoxic reaction before treatment was median 10 and under treatment median 6 (IQR 3-7). QoL at the end of the observation period in 2018 (with all the assessed patients under treatment) was 81.4% (IQR 69.4-93.4, n = 34). A 97.4% treatment adherence rate was observed. CONCLUSION: Treatment of EPP patients with afamelanotide is highly effective under real-world conditions. We suggest PBTT as a clinical meaningful endpoint in further clinical trials.
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Quemaduras , Protoporfiria Eritropoyética , Humanos , Protoporfiria Eritropoyética/tratamiento farmacológico , Calidad de Vida , alfa-MSH/análogos & derivadosRESUMEN
The novel group of immunological agents used for solid tumors has importantly improved the quality of life and the survival rate of oncologic patients. Compared to conventional chemotherapy agents, they are more effective and less toxic. However, adverse cutaneous effects are commonly observed, and in some cases, they may induce treatment discontinuation, with heavy impact on patient prognosis. Among these, photosensitive reactions, either phototoxic or photoallergic, are increasing. Much remains to be clarified on the understanding of their prevention, diagnosis, and management. We have reviewed the literature about photosensitive reactions occurring during oncologic immunotherapies. Early dermatological diagnosis and adequate management, with oncologist's cooperation, is fundamental.
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Antineoplásicos Inmunológicos/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Trastornos por Fotosensibilidad/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Humanos , Trastornos por Fotosensibilidad/terapiaRESUMEN
Phototoxic reaction is a known feature of EPP at least in part triggered by the oxidative status, complement system activation, and mast cell response. The aim of this study was to verify some aspects involved in phototoxic reaction during a season. The complement system was evaluated by C3 assay, alternative pathway by factor-B, and classical pathway by C1q; oxidative status was tested with malondialdehyde (MDA) and mast cell by IL-10 assay. The serum samples were collected in winter and summer from 19 EPP patients and 13 controls. The reaction to sun exposure within each group was monitored without any invasive treatment. In summer, C3 and factor B were higher in patients than in controls (p = 0.002 and < 0.0001 respectively), while no change was detected for C1q. The oxidative stress was increased in summer in comparison with the control group (p = 0.04), and IL-10 an assay was normal in both seasons. The correlation between the C3 and factor-B in summer was significant. This study shows that the phototoxic reaction is not limited to the dermis but can also exert a systemic response, which could affect the general health of a patient. The knowledge of the pathophysiology of phototoxic reaction is essential for identifying new disease markers useful for improving clinical studies of known and future drugs.
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Proteínas del Sistema Complemento , Dermatitis Fototóxica , Interleucina-10 , Malondialdehído , Mastocitos , Protoporfiria Eritropoyética , Adulto , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Dermatitis Fototóxica/sangre , Dermatitis Fototóxica/inmunología , Dermatitis Fototóxica/patología , Femenino , Humanos , Interleucina-10/sangre , Interleucina-10/inmunología , Masculino , Malondialdehído/sangre , Malondialdehído/inmunología , Mastocitos/inmunología , Mastocitos/metabolismo , Mastocitos/patología , Persona de Mediana Edad , Estrés Oxidativo/inmunología , Protoporfiria Eritropoyética/sangre , Protoporfiria Eritropoyética/inmunología , Protoporfiria Eritropoyética/patología , Estaciones del Año , Luz Solar/efectos adversosRESUMEN
A phototoxic reaction may be induced by additional exposure to solar radiation during photochemotherapy (psoralen, ultra-violet A - PUVA treatment). A woman was admitted to Dermatology and Venereology Clinic in Lódz as an emergency case due to extensive erythematous-vesicular lesions on the skin of the lower limbs, accompanied by pain, itching and burning of the skin. The interview found that the patient was undergoing PUVA phototherapy for psoriatic lesions, with hypertension and nicotine dependence. Physical examination revealed large blisters, filled with serum and congestive erythematous lesions located on the lateral surfaces of the thighs and backs of the feet, as well as marked swelling of the lower limbs. Also, discs coated with thin scales were found on the upper and lower limbs and on the trunk. The entire body was intensely tanned. The patient was diagnosed with acute phototoxic reaction and general corticosteroids, antihistamine drugs, an antibiotic, antihypertensive drugs and topical treatment were introduced. Immunological tests were performed during the first days of hospitalization following the emergence of new blisters. Negative results ruled out bullous pemphigoid and pemphigus. Gradual clinical improvement was observed. To avoid the occurrence of acute phototoxicity during phototherapy, patients require education about the need to avoid UV exposure and to use photoprotection, when receiving UV-sensitizing treatment. Med Pr. 2019;70(6):763-8.
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Corticoesteroides/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Dermatitis Fototóxica/etiología , Dermatitis Fototóxica/terapia , Terapia PUVA/efectos adversos , Exposición a la Radiación/efectos adversos , Dermatitis Fototóxica/diagnóstico , Femenino , Humanos , Resultado del TratamientoRESUMEN
Vandetanib is a tyrosine kinase inhibitor approved by the United States Food and Drug Administration for the treatment of metastatic medullary thyroid cancer. It has been linked to a variety of dermatologic reactions, including photosensitivity. We describe the case of a 55-year-old man who developed a severe, painful, erythematous, bullous eruption in sun-exposed areas one month after the initiation of vandetanib. The eruption was initially refractory to treatment with steroids and did not resolve with strict sun avoidance, but finally cleared after a few weeks of oral supplementation with Polypodium leucotomos (P. leucotomos) extract. P. leucotomos is an extract derived from a tropical fern, with antioxidant effects that mitigate ultraviolet-induced cutaneous erythema via inflammatory interference and the promotion of other cytotoxic responses. This case illustrates the potential for P. leucotomos to be used as a safe and effective photoprotective agent for refractory phototoxic reactions. Further randomized, controlled trials are needed to better understand the mechanism of action and photoprotective properties of P. leucotomos in the treatment of tyrosine kinase-induced phototoxicity and other dermatoses.
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Phototoxicity occurs when the effects of sunlight and certain drugs converge at the skin level. Various pharmacologic agents have been linked to photosensitivity, including agents used in hematology and oncology. We describe herein a severe phototoxic response to subcutaneous 5-azacitidine. There are no previous reports of phototoxicity reactions to this agent in the published literature. As 5-azacitidine is frequently used to treat patients with myelodysplastic syndromes and acute myeloblastic leukemia, familiarity with this side effect is important for the medical and scientific community at large.
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Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/efectos adversos , Dermatitis Fototóxica/etiología , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológicoRESUMEN
Phototoxic reaction has not been reported previously as an adverse reaction to the combination of atovaquone and proguanil (AP) (Malarone) used for antimalarial prophylaxis and therapy. We report here a 32-year-old patient treated with AP who presented with clinical manifestations of photosensitivity. AP-induced phototoxicity in this patient was further supported by phototesting. Malarone is not known to photosensitize and render the skin more susceptible to severe sunburn-like reactions. That it may do so, as in this case, is of importance especially as this drug is used predominantly by those travelling to sunnier climes. A notification of potential phototoxic effects of AP should be published for the choice of prophylaxis made by tourists traveling in malarial areas.
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Antimaláricos/efectos adversos , Atovacuona/efectos adversos , Dermatitis Fototóxica/etiología , Proguanil/efectos adversos , Adulto , Dermatitis Fototóxica/diagnóstico , Dermatitis Fototóxica/patología , Combinación de Medicamentos , Humanos , Malaria/prevención & control , Masculino , ViajeRESUMEN
A 49-year-old male had erythematous to rusky red papules, indurated plaques and lichenified patches with hyperpigmentation on sun-exposed areas for 6 years. Phototest revealed the decreased rninimal erythemal dose to UVA(10J/cm. Photopatch test with 5% Trandate ointment, 5% hydrochlorthiazide ointment and vaselin. as a control were all negative. Two weeks after cessation of Trandate, an oral challenge of hydrochlorthiazide followed by phototest was perfrirmed resulting in exacerbation of skin lesions and photosensitivity with a decreased MED to UVA(10J/cm) again. After the cesation of Trandate containing hydrochlorthiazide, the skin lesions were improved with complete loss of photosensitivity. But, improvement of the infiltrated or licheified plaques were delayed. Presenile cataract previously noted in the patient seemed to be related to his longstanding intake of hydrochlorthiazide.
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Humanos , Masculino , Persona de Mediana Edad , Catarata , Hiperpigmentación , Labetalol , PielRESUMEN
We report a case of a phototoxic reaction in a 48-year-old female induced by griseofulvin ingestion. The patient hac! erythematous papules, vesicles and patches on the sun-exposed areas. Phototest revealed a decreased minimal erythemal dose to UVA (10J/cm). Photopatch tests with 1%, 5%, 10% Griseofulvin ointment and vaseline as a control and photoingestion tests with Griseofulvin (50mg b.i.d.) were all negative. After the cessation of Griseofulvin, her skin lesions were markedly improved with complete loss of photosensitivity.