Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

A real-life comparison of pulmonary and nasal outcomes in patients with severe asthma and nasal polyposis treated with T2-biologics.

Background: Severe asthma (SA) with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with type 2 (T2) inflammatory endotype. Consequently, therapeutic targets are T2 biologics. The present retrospective study aimed to analyze and compare the clinical efficacy of mepolizumab, benralizumab, omalizumab, and dupilumab in patients with SA and comorbid CRSwNP. Methods: 115 adult patients with SA and CRSwNP receiving 1 of the 4 biologics (mepolizumab n = 31; benralizumab n = 27; dupilumab n = 27; omalizumab n = 30) were included in the retrospective open monocentric study. Pulmonary and rhinological parameters were evaluated by Asthma Control Test (ACT), FEV1%, GINA-severity grade, rhinological questionnaires (CRS VAS-scores and sinonasal QoL RSOM-31) before and after 4-6 months of therapy. Results: After 4-6 months of therapy, the Asthma Control Test and FEV1% significantly improved in all biologics groups (p < 0.01). GINA-score significantly improved in the omalizumab group only (p < 0.01). Overall, most nasal scores measured by VAS, total and nasal RSOM-31 subscores improved in all treatment groups (p < 0.05). Interestingly, the most significant differences in pre/post scores were observed in the patients receiving dupilumab, with the most notable improvement for all nasal symptoms, RSOM-31 total score, and RSOM-31 nasal subscore. There were no significant changes in the VAS scores loss of smell in the benralizumab group and postnasal drip in the mepolizumab group. Conclusion: T2-targeting biologics effectively treat asthma in patients with severe asthma and comorbid CRSwNP. However, the efficacy of T2 biologics differs regarding the outcome in CRSwNP.

Chemokine Expression-Based Endotype Clustering of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) with (CRSwNP) or without nasal polyps (CRSsNP) is a persistent, heterogeneous inflammatory condition affecting the upper respiratory tract. The present study aimed to improve the characterization of CRS endotypes based on the chemokine and cytokine expression pattern in the CRS tissues. Concentrations of chemokines and cytokines were measured in tissues from nasal biopsies obtained from 66 CRS patients and 25 control subjects using multiplexing or single analyte technologies. Cluster analysis based on the concentration of type-1 (MCP-3/CCL7, MIP-1 α/CCL3), type-2 (IL-5, MCP-3/CCL7, MIP-1 α/CCL3, TARC/CCL17, PARC/CCL18, IP-10/CXCL10, ECP), and type-3 (IL-22) chemokines and cytokines identified six CRS endotypes (clusters). Cluster 1 (type-3) and 2 (type-1) were associated with a low prevalence of nasal polyps, Cluster 3 (type-1, -2, -3) and Cluster 4 (type-2, -3, medium IL-22) with medium, and Cluster 5 (type-2, -3, high Il-22) and Cluster 6 (type-2) with high prevalence of nasal polyps. Asthma was highly prevalent in Cluster-6. Our findings add to the existing knowledge of CRS endotypes and may be useful for the clinical decision-making process. The advancement of biologics therapy for upper respiratory tract disorders rationalizes the personalized diagnostic approach to warrant a successful treatment and monitoring of CRS.

The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers.

Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different antigens, including allergens and microbial pathogens. MCs can produce and respond to physiological mediators and chemokines to modulate inflammation. As long-lived, tissue-resident cells, MCs indeed mediate acute inflammatory responses such as those evident in allergic reactions. Furthermore, MCs participate in innate and adaptive immune responses to bacteria, viruses, fungi, and parasites. The control of MC activation or stabilization is a powerful tool in regulating tissue homeostasis and pathogen clearance. Moreover, MCs contribute to maintaining the homeostatic equilibrium between host and resident microbiota, and they engage in crosstalk between the resident and recruited hematopoietic cells. In this review, we provide a comprehensive overview of the functions of MCs in health and disease. Further, we discuss how mouse models of MC deficiency have become useful tools for establishing MCs as a potential cellular target for treating inflammatory disorders.

Epidermal carotenoid levels in vivo of patients with plaque psoriasis: Effects of narrow-band UVB phototherapy.

BACKGROUND: Psoriasis is a systemic inflammatory disease characterized by hindered antioxidant defense and increased formation of free radicals. There are limited data on the skin carotenoids in psoriatic skin as well as their modulation during narrow-band UVB (NB-UVB) phototherapy of the disease. AIM: The aim of this prospective study is to reveal the skin carotenoids levels during NB-UVB phototherapy of psoriasis in humans. MATERIAL AND METHODS: Twenty Caucasian subjects with mild-to-moderate plaque psoriasis (15m; 5f) were enrolled in the study, and nine gender- and age-matched healthy volunteers were recruited for controls of oxidative stress measurements. All psoriasis patients underwent 10 sessions of NB-UVB phototherapy. Measurements were taken at baseline and after 10 sessions of NB-UVB phototherapy. The assessment of carotenoid levels in the skin in vivo was performed by a non-invasive, reflectance spectroscopy-based device. Psoriasis severity was assessed by psoriasis area and severity index (PASI). The dermatology life quality index (DLQI) was evaluated in psoriatic patients. RESULTS: Baseline carotenoid levels were significantly lower in psoriasis patients in comparison to healthy controls. NB-UVB phototherapy insignificantly diminished carotenoid levels in the skin of psoriasis patients, while clinical improvement both in PASI score and DLQI was observed. CONCLUSION: We showed the levels of skin carotenoids in psoriatic patients are lower than in healthy subjects. NB-UVB did not change significantly skin carotenoid levels. Further studies should elucidate the potential effect of antioxidants supplementation during NB-UVB of psoriasis.

Application of parelectric spectroscopy to detect skin cancer-A pilot study.

BACKGROUND: The early detection of skin cancer is still challenging and calls for objective, fast diagnostic, and ideally non-invasive methods in order to leave the potentially malignant tumor cells unaltered. In this paper, the parelectric spectroscopy was applied to evaluate the potential of a non-invasive detection of basal cell carcinoma (BCC) and malignant melanoma. MATERIALS AND METHODS: A prototype of parelectric spectroscopy was used to investigate non-invasively dipole density and mobility of suspicious skin lesions. The differences in investigated tissue were analyzed compared to pathohistological findings in a clinical study on 51 patients with suspected BCC and malignant melanoma. RESULTS: The non-invasive parelectric spectroscopy could differentiate between normal skin, BCC, and melanoma but failed to distinguish between different types of skin cancer. The data were normalized to unsuspected nearby skin because the different skin locations influence dipole density and mobility. CONCLUSION: The results of the pilot study indicate that the parelectric spectroscopy might be an additional, useful non-invasive diagnostic procedure to distinguish between normal skin and skin cancer.

Guia prático da Associação Brasileira de Alergia e Imunologia para o diagnóstico e tratamento das urticárias baseado em diretrizes internacionais / A practical guide of the Brazilian Association of Allergy and Immunology to the diagnosis and treatment of urticaria based on international guidelines

A urticária crônica espontânea afeta mais de um milhão de brasileiros e impacta significativamente em sua qualidade de vida. Para atualizar as recomendações quanto ao seu diagnóstico e tratamento, especialistas de todo o mundo reúnem-se a cada quatro anos em Berlim e revisam todas as novas evidências que justifiquem modificações na diretriz internacional. Este artigo discute as principais recomendações propostas na versão atual da diretriz.

Chronic spontaneous urticaria affects more than one million Brazilians and significantly impacts their quality of life. In order to update the recommendations on diagnosis and treatment, experts from all over the world meet every 4 years in Berlin to review all the new evidence that can support modifications to the international guidelines. This paper discusses the main recommendations proposed in the current version of the guidelines.

Epidermal barrier and oxidative stress parameters improve during in 311 nm narrow band UVB phototherapy of plaque type psoriasis.

BACKGROUND: Psoriasis is a multi-systemic inflammatory disease that results from dysregulation between epidermal keratinocyte homeostasis and both innate and acquired immunity. Epidermal barrier defect has been described in psoriatic lesions. Furthermore an imbalance between pro-oxidative stress and antioxidant defense mechanisms are known in psoriasis patients. AIM: The aim of this study was to address the link between disease activity, epidermal barrier and systemic oxidative stress in the course of 311 nm narrow band ultraviolet B (NB-UVB) therapy of psoriasis. The dynamic of systemic oxidative stress parameters as well as local transepidermal water loss (TEWL) and stratum corneum hydration (SCH) was characterized before and after 311 nm NB-UVB therapy on the plaques of psoriasis vulgaris in comparison to untreated non-affected volar forearm sites of the same patients. MATERIAL AND METHODS: 22 patients with plaque type psoriasis vulgaris and 25 gender- and age-matched healthy controls were enrolled. We assessed the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) for monitoring disease activity, severity and self-perceived DLQI impact as patient related outcome parameter. We measured non-invasively TEWL (Tewameter TM 300) and SCH (Corneometer CM 825) and the end product of lipid peroxidation - malondialdehyde (MDA), Reactive oxygen species (ROS), ascorbyl radicals (Asc) and detoxifying activity of catalase (CAT) were measured in the peripheral blood with spectrophotometric and EPR spectroscopy methods. RESULTS: Disease activity improved in all patients compared to baseline witnessed by significant decrease in PASI; (from 14.1 to 10.4; p < 0.0001) and DLQI (from 11.7 to 8.1; p < 0.0001). At baseline TEWL-values were significantly (p < 0.0001) higher on psoriatic plaques (16.8 g/h/m2) in comparison to uninvolved skin (5.3 g/h/m2); with a decrease at both sites after NB-UVB phototherapy. SCH was significantly lower at psoriatic plaque s (4.7AU) compared to uninvolved sskin (42.4AU) and increased after treatment (8.6AU) (p < 0.0001). Interestingly, SCH decrease slightly during therapy at uninvolved skin (40.6AU). ROS and Asc declined during therapy in parallel to a decrease in MDA. A mild decrease in the antioxidative enzyme CAT activity which did not reach the significance was observed. CONCLUSION: The presented data is shows that a clinical improvement of psoriatic plaques under NB-UVB therapy, shown in with a decreased PASI and reflected by an increase in quality of life has beneficial effects on epidermal barrier function, SCH and improvement of systemic oxidative stress parameters (ROS, MDA and Asc). We assume that the general improvement in the oxidative stress parameters along with epidermal barrier parameters reflects mainly the improvement of disease activity which overwrites the possible negative pro-oxidative effects of the UV treatment.

In Situ Deactivation of Interleukin-6 Enhances Early Peripheral Nerve Regeneration in a Murine Injury Model.

BACKGROUND: Systemic alteration of interleukin-6 (IL-6) influences peripheral nerve regeneration. We investigated the potential influences of in situ (at the coaptation site) IL-6 modulation in a peripheral-nerve-transection/sciatic-nerve-graft in vivo model. METHODS: We quantified the elongation of regenerating axons, the number of arborizing axons, and the number of branches per arborizing axon 7 days after the injury in mice expressing axonal fluorescent proteins (thy-1-YFP mice). Sciatic nerves from nonexpressing mice (C57Bl6 or IL-6(-/-) mice) were grafted into those expressing yellow fluorescent protein. We altered the in situ IL-6 concentration by loading a topical gelatin sponge with an inhibiting IL-6 receptor antibody or IL-6 combined with a soluble IL-6 receptor. Sciatic nerves from IL-6(-/-) mice were grafted into an additional group. The contralateral sham-operated side served as control in all the groups. RESULTS: Axonal elongation increased significantly with the in situ application of the IL-6 receptor antibody, while topical IL-6 significantly reduced the regeneration distance. The number of arborizing axons increased significantly in nerves grafted from IL-6(-/-) mice, whereas branches per arborizing axons remained stable. CONCLUSION: In situ IL-6 receptor inhibition and IL-6(-/-) nerve grafting enhance early peripheral nerve regeneration in an acute murine injury model.

In vivo study for the discrimination of cancerous and normal skin using fibre probe-based Raman spectroscopy.

Raman spectroscopy has proved its capability as an objective, non-invasive tool for the detection of various melanoma and non-melanoma skin cancers (NMSC) in a number of studies. Most publications are based on a Raman microspectroscopic ex vivo approach. In this in vivo clinical evaluation, we apply Raman spectroscopy using a fibre-coupled probe that allows access to a multitude of affected body sites. The probe design is optimized for epithelial sensitivity, whereby a large part of the detected signal originates from within the epidermal layer's depth down to the basal membrane where early stages of skin cancer develop. Data analysis was performed on measurements of 104 subjects scheduled for excision of lesions suspected of being malignant melanoma (MM) (n = 36), basal cell carcinoma (BCC) (n = 39) and squamous cell carcinoma (SCC) (n = 29). NMSC were discriminated from normal skin with a balanced accuracy of 73% (BCC) and 85% (SCC) using partial least squares discriminant analysis (PLS-DA). Discriminating MM and pigmented nevi (PN) resulted in a balanced accuracy of 91%. These results lie within the range of comparable in vivo studies and the accuracies achieved by trained dermatologists using dermoscopy. Discrimination proved to be unsuccessful between cancerous lesions and suspicious lesions that had been histopathologically verified as benign by dermoscopy.

Perturbation factors in the clinical handling of a fiber-coupled Raman probe for cutaneous in vivo diagnostic Raman spectroscopy.

The application of fiber-coupled Raman probes for the discrimination of cancerous and normal skin has the advantage of a non-invasive in vivo application, easy clinical handling, and access to the majority of body sites, which would otherwise be limited by stationary Raman microscopes. Nevertheless, including optical fibers and miniaturizing optical components, as well as measuring in vivo, involves the sensibility to external perturbation factors that could introduce artifacts to the acquired Raman spectra and thereby potentially reduce classification performance. In this study, typical perturbation factors of Raman measurements with a Raman fiber probe, optimized for clinical in vivo discrimination of skin cancer, were investigated experimentally. Measurements were performed under standardized conditions in clinical settings in vivo on human skin, as well as ex vivo on porcine ears. Raman spectra were analyzed in the fingerprint region between 1150 and 1730 cm(-1) using principal component analysis. The largest artifacts in the Raman spectra were found in measurements performed under the influence of strong ambient light conditions as well as after miscellaneous pre-treatments to the skin, such as use of a permanent marker or a sunscreen. Minor influences were also found in measurements using H2O immersion and when varying the probe contact force. The effect of reasonable variation of the fiber-bending radius was found to be of negligible impact. The influence of measurements on hairy or sun-exposed body sites, as well as inter-subject variation, was also investigated. The presented results may serve as a guide to avoid negative effects during the process of data acquisition and so avoid misclassification in tumor discrimination.

Efficient prevention strategy against the development of a palmar-plantar erythrodysesthesia during chemotherapy.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a highly efficient chemotherapeutic; however, it induces dermal side effects such as palmar-plantar erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with the sweat onto the skin surface. AIM: The aim of the present study was to examine whether a topically applied ointment containing antioxidants with a high radical protection factor is able to prevent the formation of PPE. METHODS: Twenty patients suffering from ovarian carcinoma and treated with PLD were observed. RESULTS: 60% of the patients tolerated the regular application of the cream and developed no PPE. The remaining 40% interrupted the application. Six of them developed PPE and resumed ointment application thereafter. In these cases the PPE disappeared or was strongly reduced. CONCLUSION: The results of the observation clearly demonstrate that topical application of the ointment is an efficient strategy against the development of PPE during chemotherapy with PLD.

Acute irritant threshold correlates with barrier function, skin hydration and contact hypersensitivity in atopic dermatitis and rosacea.

The aim of the study was to disclose interactions between epidermal barrier, skin irritation and sensitization in healthy and diseased skin. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients with atopic dermatitis (AD), rosacea and healthy controls. A 4-h patch test with seven concentrations of sodium lauryl sulphate was performed to determine the irritant threshold (IT). Contact sensitization pattern was revealed by patch testing with European baseline series. Subjects with a lower IT had higher TEWL values and lower SCH. Subjects with positive allergic reactions had significantly lower IT. In AD, epidermal barrier deterioration was detected on both volar forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters were observed on the facial skin only, suggesting that barrier impediment is restricted to the face in rosacea, in contrast with AD where the abnormal skin physiology is generalized.

Optical coherence tomography for presurgical margin assessment of non-melanoma skin cancer - a practical approach.

In the clinical setting, optical coherence tomography (OCT) is applicable for the non-invasive diagnosis of skin cancer and may in particular be used for margin definition prior to excision. In this regard, OCT may improve the success rate of removing tumor lesions more effectively, preventing repetitive excision, which may subsequently result in smaller excisions. In this study, we have aimed to evaluate the applicability of OCT for in vivo presurgical margin assessment of non-melanocytic skin tumors (NMSC) and to describe the feasibility of different scanning techniques. A total number of 18 patients planned for excision of lesions suspicious of NMSC were included in this study. Based on OCT, we defined the specific tumor margins on 19 lesions preoperatively using different scanning modalities. Sixty-one margin points and five complete tumor margins were analysed on 18 patients with a total of 19 lesions including 63% basal cell carcinoma (BCC) (n = 12), 16% (n = 3) squamous cell carcinoma (SCC) and 21% of other types of skin tumors (n = 4) were classified. In 84% of the cases (n = 16), the OCT-defined lateral margins correctly indicated complete removal of the tumor. The surgical margins chosen by the surgeon never fell below the OCT-defined margin. Regarding the techniques of marginal definition, punctual tumor border scan in the perpendicular direction, with an extension of free-run scans for unsure cases can hardly be recommended. This study shows that suspected NMSC can effectively be confirmed, and furthermore, resection margin can be minimized under OCT control without reducing the rate of complete removal.

Optical coherence tomography-based optimization of mohs micrographic surgery of Basal cell carcinoma: a pilot study.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive imaging technique that uses a low-power infrared laser to image up to 2 mm beneath the skin's surface. OBJECTIVE: To test the feasibility and diagnostic value of using in vivo OCT to define excision margins before Mohs micrographic surgery (MMS) of basal cell carcinoma (BCC). METHODS: Patients with biopsy confirmed BCC undergoing MMS were recruited (n = 52). Excision margins defined by experienced dermatologists were compared with those of OCT-assessed borders and validated with histologic assessments. RESULTS: Forty-one (79%) lesions were clear after one MMS procedure; 11 (21%) lesions required a second MMS stage after excision of the clinician-predicted boundary. Generally, the OCT instrument indicated that the estimated clinical margin was 0.4-mm larger than the OCT margin. For lesions requiring a single MMS stage, OCT indicated that lesions were 1.4 ± 1.3 mm smaller than the Mohs excision. Before excision of lesions requiring more than one MMS stage, OCT always indicated that the lesion boundary would extend outside the planned MMS defect boundary. CONCLUSIONS: The present study shows the prospective utility of using OCT to refine clinically estimated borders for MMS. OCT assessment has the potential to reduce the excised area without compromising the integrity of tumor-free borders.

Management of anticoagulation during dermatosurgical procedures in Germany - results from a cross-sectional study.

BACKGROUND: Treatment with antiplatelet drugs (APD) and vitamin K antagonists (VKA) can be a challenge during the management of dermatosurgical interventions. METHODS: We performed a cross-sectional study on the perioperative management of APD and VKA in dermatological private practices and clinics in Germany, using anonymized, standardized questionnaires. RESULTS: 233 responses were evaluated (response rate 37 %). Skin biopsies are performed in 82.7 % of offices and in 90.8 % of clinics despite treatment with VKA. Small excisions are done in 62.5 % of offices and 76.9 % of clinics during treatment with VKA, for large excision this applies to 11.9 % of offices and 33.8 % of clinics. Low-dose treatment with APD (#100 mg) does not hinder 80.4 % of private practices and 89.2 % of clinics to perform small excisions as well as 36.3 % and 53.8 %, respectively, to perform large excisions. Of private practitioners 67.3 % and 83.1 % of clinic-based dermato-surgeons do not consider high-dose APD a contraindication for small excisions, and 25.0 % and 41.5 %, respectively, for large excisions. Most frequently switching to heparin is performed 6-8 days prior to surgery and switching back 0-2 days after surgery. CONCLUSIONS: Large differences in the perioperative management of anticoagulant therapy during dermatosurgical procedures have been identified. Further studies and guidelines should be developed.

Photodynamic therapy in dermatology: past, present, and future.

Photodynamic therapy (PDT) is a noninvasive therapeutic method first introduced in the field of dermatology. It is mainly used for the treatment of precancerous and superficial malignant skin tumors. Today PDT finds new applications not only for nononcologic dermatoses but also in the field of other medical specialties such as otorhinolaryngology, ophthalmology, neurology, gastroenterology, and urology. We are witnessing a broadening of the spectrum of skin diseases that are treated by PDT. Since its introduction, PDT protocol has evolved significantly in terms of increasing method efficacy and patient safety. In this era of evidence-based medicine, it is expected that much effort will be put into creating a worldwide accepted consensus on PDT. A review on the current knowledge of PDT is given, and the historical basis of the method's evolution since its introduction in the 1900s is presented. At the end, future challenges of PDT are focused on discussing gaps that exist for research in the field.