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The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field.

This second part of the article aims to highlight recent contributions in the literature that enhance our understanding of the cutaneous immune response to allergen. Several properties of allergens facilitate barrier disruption and cutaneous sensitization. There is a strong epidemiologic relationship between the microbiome, both the gut and skin, and atopic dermatitis (AD). The mechanisms connecting these two entities remain enigmatic; however, recent murine models show that commensal skin bacteria play an active role in supporting skin barrier homeostasis and defense against microbial penetration. Likewise, the association between the lack of colonization with Staph species and AD development suggests a potentially functional role for these organisms in regulating the skin barrier and response to environmental allergens. In undisrupted skin, evidence suggests that the cutaneous route may promote allergen tolerance. Properties of environmental allergens and commensal bacteria add to the complex landscape of skin immunity. Further investigation is needed to elucidate how these properties regulate the cutaneous immune response to allergen.

Mucormycosis is an infection caused by fungi belonging to class zygomycetes, with high mortality and morbidity rate. Acquisition of mucormycosis is inhalation of spores or cutaneous route. The common risk factors for invasive mucormycosis consist of diabetes mellitus, high-dose glucocorticoid therapy, and neutropenia. The most clinical manifestation of mucormycosis is rhinocerebral lesions. Other manifestations are pulmonary, cutaneous, disseminated, and gastrointestinal. Ear involvement is extremely rare. The authors describe a case of mucormycosis cholesteatoma with concomitant central nervous system lesion in a patient with diabetes mellitus that responded to therapy.

Rationale: Corrosion refers to the degradation of a material that occurs following its interaction with other substances in the environment. Corrosion of metallic substances into tissues may lead to inflammatory responses such as systemic contact dermatitis (SCD), a skin condition where an individual who has previously been sensitized to a particular allergen via the cutaneous route will subsequently react to same allergen via the systemic route. This condition occurs following exposure to allergens such as metals, medications, and certain food substances. In recent years, the use of metal plates for internal fixation has become increasingly common in bone fracture repairs. Patient concerns: A 34-year-old Indonesian male presented with systemic erythema with itching 7 days following a bone plate fixation as a management for mandibular fracture. Diagnoses: Physical examination showed pruritic red macules, papules, and scales on almost his entire body, along with facial swelling. The patch test results revealed a positive reaction to nickel and cobalt. Therefore, the patient was diagnosed with SCD. Interventions: The patient was treated with topical and systemic corticosteroids as well as bone plate removal. Outcome: After treatment, the eruption turned brown, the itching was resolved, and there were no facial swelling as well. Lessons: This case report highlights the need to consider the occurrence of SCD in patients following bone plate fixation.

Treatment of infections largely encompasses the field of dental medicine. Prevention and management of infection in the oral and maxillofacial region involve every facet of dental care that may be necessary due to caries, periodontal disease, pulpal pathology, trauma, reconstructive and surgical implants. One of the first surgical procedures in the treatment of localized infection commenced with the opening of bulbous abscesses with sharp stones and pointed sticks. The principles for the management of infection basically remain the same although the surgical technique has remarkably improved. It takes a qualitative and quantitative amount of bacterial insult to produce a certain degree of infection that may eventually lead to facial swelling, asymmetry, discomfort and loss of function. In the oral cavity and its surrounding structures, the predominant organisms such as the staphylococci and streptococci release enzymes responsible for the breakdown of fibrin (connective tissue ground substances) and lyse cellular debris, which facilitates a rapid spread of infection. At the University of the Philippines, Philippine General Hospital Medical Center, where I have served for 18 years, 90% of dental consultations from the outpatient department and emergency room complex concern infection, and 85% of facial swelling is dental in origin. A typical odontogenic infection is a dentoalveolar abscess that spreads deeply into the soft tissue rather than exiting superficially through the oral and cutaneous route, consequently involving the fascial spaces. Following the path of least resistance through connective tissue and along fascial planes, infection may diffuse quite distantly from its dental source, causing damage to the surrounding structures. Appreciation not only of the anatomy of the face and neck is necessary to predict sufficiently the pathway of spread of these infections, but also knowledge of how to drain these spaces adequately.

were available for examination. Because respiration can occur through both the lungs and the skin of frogs, there may have been a cutaneous route of infection in these frogs; however, hematogenous spread to muscle tissue via inhalation or ingestion of conidia cannot be excluded. As is often seen in other species, inflammatory reaction to the organisms in the frogs was nonexistent and consisted only of fibrosis surrounding the organisms.

Methomyl, a potent anticholinesterase carbamate insecticide, is markedly toxic in man following suicidal ingestion. Thirteen cases of acute field-poisonings in rural workers after spraying methomyl reported to the Lyon Poison Centre demonstrate that poisoning can occur following occupational exposure. In this setting, the cutaneous route is critical. Although recovery was obtained uneventfully within 48 h in all cases, preventive measures are essential to avoid accidental poisonings. Copyright © 1999 John Wiley & Sons, Ltd.

Mycobacterium szulgai is a ubiquitious non-tuberculous mycobacterium causing infection in immunocompetent and immunocompromized patients. Clinically mimicking pulmonary tuberculosis in most cases described, rarely other manifestations occur. Here we report the case of an AIDS patient with osteomyelitis of the hand and toe, accompanied by multiple cutaneous ulcers of the chest and forearm. The case highlights the unusual combination of osteomyelitis and skin ulcers without pulmonary infection and describes the likely cutaneous route of infection in a patient who keeps tropical fish.

Infectious diseases remain serious public health problems in the tropics and semi-tropics, which are exposed to high levels of UVB in sunlight. The UVB flux at the equator is one to four watts per square meter, so that even the highest experimentally effective doses can be acquired in several hours’ exposure to midday sun. UVB is a potent suppressor of cell-mediated immunity. Many infectious diseases are acquired via the cutaneous route and protection is mediated by cellular immunity in immunocompetent individuals. In animal models for several such infectious diseases, UVB irradiation alters pathogenesis and immunity. In a murine model for cutaneous leishmaniasis, UVB irradiation applied during the first exposure to Leishmania altered the pathology of primary skin lesions, abrogated the induction of protective immunity, and may have predisposed the mice to fatal systemic leishmaniasis. UVB irradiation of mouse skin causes a spectrum of immunological and fine structural alterations also seen in human skin. Therefore, it is likely that exposure to high levels of solar UVB may enhance severity and adversely affect protective immune responses in naturally acquired infectious diseases of humans.

In the establishment of workplace exposure standards, the potential for cutaneous absorption is taken into consideration through the addition of "skin notation" to the relevant substance. In the TLVs Documentation (ACGIH, 1986) dermal lethal dose to 50% (LD50) or human data are the bases for the assignment of "skin notation" to 91 of 168 substances. For the other substances, the "skin" attribution seems to be based on undocumented statements in 24 (14.5%), skin effects in 13 (8%), and analogy in 7 (4%), while in the remaining 33 (20%) any reference is lacking as to the basis for notation of the cutaneous route of entry. Furthermore, since the established "cut-off" value of 2 g/kg is sometimes bypassed when a notation is added or omitted, the use of dermal LD50 is perplexing. Given the relevance of the skin notation for the validation of threshold limit values (TLVs) in the workplace, a full examination and citation of all available scientific data are recommended when establishing the TLV of substances absorbable through the skin.

C3Hf/HeN or BALB/c mice, exposed to acute ultraviolet (UV) irradiation and skin-sensitized through the irradiated skin site with soluble protein antigens, exhibit humoral tolerance to subsequent systemic challenge with antigen. We have termed this phenomenon "phototolerance" (PT). With the doses of UV radiation used, PT induction is restricted to the irradiated skin site and is observed only if sensitization is performed via the cutaneous route. PT is antigen specific and operates at the afferent level of the immune response. While single PT induction regimens result in transient humoral suppression, multiple inductions before each systemic challenge can maintain the response at low levels. The capacity to induce PT to a variety of soluble protein antigens may have potentially important clinical applications.

For a number of years one of us (Meyer)1 has attempted to analyze the mechanism of the immunity response which follows an intracutaneous injection of filtrates, vaccines, etc. It appeared superfluous to study the phenomena more carefully until the facts reported by Besredka and his followers 2 with human pathogenic microbes mostly noninvasive by the cutaneous route had been confirmed with organisms responsible for spontaneous infections in laboratory animals. Furthermore, since Besredka stresses the importance of organotropism for various bacteria it appeared desirable to ascertain if it might be possible to cuti-immunize either locally or generally against an organism for which the skin is in all probability not the receptive tissue. An enterotropic organism, B. aertrycke (B. enteritidis Breslau, B. pestis caviae) of guinea-pigorigin which caused general infections when fed and when injected intracutaneously was chosen for the study to be reported in this communication.

Summary and Conclusions 1. Experiments concerning the mechanism of transmission in man of Chinese relapsing fever have been performed on 6 normal subjects and 4 patients with general paralysis of the insane. 2. The bites of lice infected with the Chinese strain of Borrelia recurrentis are not infective to man. 3. The feces of lice infected with Bor. recurrentis are not infectious to man. 4. Man contracts relapsing fever through crushing the infected lice on slightly traumatized skin such as that following louse bites and scratching, or through introducing the infective material to the conjunctivae with infected fingers. 5. On two occasions the dropping of large numbers of Bor. recurrentis onto the skin of a patient with general paralysis of the insane failed to produce relapsing fever. 6. Repeated attempts to produce relapsing fever by instilling large numbers of Bor. recurrentis onto the mucous membranes of the oral cavity failed. 7. The incubation period of relapsing fever in two patients was found to be 11 days for the cutaneous route and 8 days for the conjunctival route.

Driven by constantly increasing knowledge about skin immunology, vaccine delivery via the cutaneous route has recently gained renewed interest. Considering its richness in immunocompetent cells, targeting antigens to the skin is considered to be more effective than intramuscular or subcutaneous injections. However, circumvention of the superficial layer of the skin, the stratum corneum, represents the major challenge for cutaneous immunization. An optimal delivery method has to be effective and reliable, but also highly adaptable to specific demands, should avoid the use of hypodermic needles and the requirement of specially trained healthcare workers. The P.L.E.A.S.E.® (Precise Laser Epidermal System) device employed in this study for creation of aqueous micropores in the skin fulfills these prerequisites by combining the precision of its laser scanning technology with the flexibility to vary the number, density and the depth of the micropores in a user-friendly manner. We investigated the potential of transcutaneous immunization via laser-generated micropores for induction of specific immune responses and compared the outcomes to conventional subcutaneous injection. By targeting different layers of the skin we were able to bias polarization of T cells, which could be modulated by addition of adjuvants. The P.L.E.A.S.E.® device represents a highly effective and versatile platform for transcutaneous vaccination., Graphical abstract

Mycobacteriosis in a Phrynops hilari (side-necked turtle) was characterized by multiple caseating granulomas in the liver and spleen; pulmonary involvement did not occur. Granulomatous inflammation and organisms also were present in the skin, suggesting a cutaneous route of entry with hematogenous spread to visceral organs. Review of the four cases of chelonian mycobacteriosis in the literature indicated that pulmonary tubercules and plastral ulcerations are typical manifestations. The Mycobacterium species usually involved is M. chelonei.

Anthrax is a zoonotic disease that occurs in domesticated and wild animals. Humans become infected by contact with infected animals or contaminated products, but there are no cases of human-to-human transmission. Under natural circumstances, infection occurs by the cutaneous route and extremely rarely, by the inhalational or gastrointestinal routes. Cutaneous anthrax, the most common form is usually curable. A small percentage of cutaneous infections become systemic, and these can be fatal. An aerosol exposure to spores causes inhalational anthrax. This form of disease begins with non-specific symptoms followed in two to three days by the sudden onset of respiratory distress with dyspnea, cyanosis, and stidor. It is rapidly fatal. Treatment consists of massive doses of antibiotics and supportive care. Post exposure antibiotic prophylaxis is effective in experimental animals and should be instituted as soon as possible after exposure. A licensed nonliving vaccine is available for human use.

SUMMARYThe loss of potassium through the cutaneous route was measured in three Chokla rams by balance trial and by washing the animals (ambient temperature 28–33 °C, 28–30 mmHg vapour pressure). The excretion of potassium through urine and faeces was 46·7 and 19·4% of the intake, respectively. The excretion through skin recorded by washing the animals was 29·1% against 33·7% potassium available for excretion through the thermoregulatory route. About 2·56 g potassium was thus excreted through the cutaneous route per day. There was a net retention of 9·8 g sodium/ram/day.