Peri-implantitis with a potential axis to brain inflammation: an inferential review.

Peri-implantitis (PI) is a chronic, inflammatory, and infectious disease which affects dental implants and has certain similarities to periodontitis (PD). Evidence has shown that PD may be related to several types of systemic disorders, such as diabetes and insulin resistance, cardiovascular diseases, respiratory tract infections, adverse pregnancy outcomes, and neurological disorders. Furthermore, some types of bacteria in PD can also be found in PI, leading to certain similarities in the immunoinflammatory responses in the host. This review aims to discuss the possible connection between PI and neuroinflammation, using information based on studies about periodontal disorders, a topic whose connection with systemic alterations has been gaining the interest of the scientific community. Literature concerning PI, PD, and systemic disorders, such as neuroinflammation, brain inflammation, and neurological disorder, was searched in the PubMed database using different keyword combinations. All studies found were included in this narrative review. No filters were used. Eligible studies were analyzed and reviewed carefully. This study found similarities between PI and PD development, maintenance, and in the bacterial agents located around the teeth (periodontitis) or dental implants (peri-implantitis). Through the cardiovascular system, these pathologies may also affect blood-brain barrier permeability. Furthermore, scientific evidence has suggested that microorganisms from PI (as in PD) can be recognized by trigeminal fiber endings and start inflammatory responses into the trigeminal ganglion. In addition, bacteria can traverse from the mouth to the brain through the lymphatic system. Consequently, the immune system increases inflammatory mediators in the brain, affecting the homeostasis of the nervous tissue and vice-versa. Based on the interrelation of microbiological, inflammatory, and immunological findings between PD and PI, it is possible to infer that immunoinflammatory changes observed in PD can imply systemic changes in PI. This, as discussed, could lead to the development or intensification of neuroinflammatory changes, contributing to neurodegenerative diseases.

The Role of Salivary C-Reactive Protein in Systemic and Oral Disorders: A Systematic Review.

Background: Blood sampling is expensive, time-consuming, invasive, and requires technical facilities, which can be replaced by more convenient samples such as saliva. C-reactive protein (CRP) is a widely used biomarker in the management of many disorders and plasma CRP (pCRP) is suggested to be replaced by salivary CRP (sCRP). This study aimed to systematically review all available literature on the sCRP levels in systemic and oral disorders and how sCRP and pCRP levels correlate among these patients and healthy individuals. Methods: In this systematic review, a PubMed, Embase, Scopus, and Google Scholar search was conducted on October-2021 to identify all research investigating sCRP levels in systemic and oral disorders. Results: A total of 130 publications were analyzed in the review. Most of the studies reported that sCRP and pCRP levels are correlated, and sCRP is a reliable alternative for pCRP level for the diagnosis and management of medical conditions. sCRP has been measured in many different medical and oral disorders and significantly correlated with disease activity in most cases. Conclusion: Salivary CRP is a good alternative for Plasma CRP levels in most cases.

Mitochondriopathies as a Clue to Systemic Disorders-Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine.

The mitochondrial respiratory chain is the main site of reactive oxygen species (ROS) production in the cell. Although mitochondria possess a powerful antioxidant system, an excess of ROS cannot be completely neutralized and cumulative oxidative damage may lead to decreasing mitochondrial efficiency in energy production, as well as an increasing ROS excess, which is known to cause a critical imbalance in antioxidant/oxidant mechanisms and a "vicious circle" in mitochondrial injury. Due to insufficient energy production, chronic exposure to ROS overproduction consequently leads to the oxidative damage of life-important biomolecules, including nucleic acids, proteins, lipids, and amino acids, among others. Different forms of mitochondrial dysfunction (mitochondriopathies) may affect the brain, heart, peripheral nervous and endocrine systems, eyes, ears, gut, and kidney, among other organs. Consequently, mitochondriopathies have been proposed as an attractive diagnostic target to be investigated in any patient with unexplained progressive multisystem disorder. This review article highlights the pathomechanisms of mitochondriopathies, details advanced analytical tools, and suggests predictive approaches, targeted prevention and personalization of medical services as instrumental for the overall management of mitochondriopathy-related cascading pathologies.

Associations of pemphigus or pemphigoid with autoimmune disorders in US adult inpatients.

BACKGROUND: The associations and predictors of the gamut of autoimmune conditions in pemphigus and pemphigoid have been examined in few large-scale controlled studies. OBJECTIVE: To examine associations of pemphigus or pemphigoid with autoimmune disorders and related outcomes in adults. METHODS: Data from the 2002-2012 National Inpatient Sample were analyzed, including an ∼20% sample of all US hospitalizations (n = 72,108,077 adults). RESULTS: In multivariable logistic regression models, pemphigus (adjusted odds ratio 1.46, 95% confidence interval 1.30-1.63) and pemphigoid (adjusted odds ratio 1.35, 95% confidence interval 1.24-1.48) were associated with ≥1 autoimmune disorder. Pemphigus was associated with 9 of 29 and pemphigoid with 13 of 32 autoimmune disorders examined in bivariable models. Among pemphigus inpatients, unspecified autoimmune disease, vitiligo, eosinophilic esophagitis, and myasthenia gravis had the strongest effect sizes. Whereas, among pemphigoid inpatients, unspecified autoimmune disease, vitiligo, and chronic urticaria had the strongest effect sizes. There were significant differences of autoimmune comorbidities by age, sex, and race/ethnicity. The estimated excess annual costs of hospital care attributed to autoimmune disorders among inpatients with pemphigus was $2,286,588 and pemphigoid $4,301,681. LIMITATION: Lack of treatment history data. CONCLUSION: Inpatients with pemphigus or pemphigoid had increased odds of multiple cutaneous, extracutaneous, and systemic autoimmune disorders, which were associated with a considerable cost burden.

Relationship between apical periodontitis and atherosclerosis in rats: lipid profile and histological study.

AIM: To investigate the relationship between apical periodontitis and atherosclerosis in rats by lipid profile and carotid artery intima tunic measurement, and histological and histometric evaluation of periapical lesions. METHODOLOGY: Forty male Wistar rats were allocated into four groups: control (C), with apical periodontitis (AP), with atherosclerosis (AT) and with AP and AT (AP + AT). Atherosclerosis was induced using a high-lipid diet associated with a surgical ligature in the carotid artery and a super dosage of vitamin D3 . AP was induced via pulp exposure to the oral environment. At 45 and 75 days, serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. The maxillary and mandibular jaws and carotid artery were collected and processed for histological analysis. The Kruskal-Wallis or Mann-Whitney test was performed for nonparametric data, and the Tukey's or Student's t-test was performed for parametric data (P < 0.05). RESULTS: In nonatherosclerotic animals, the induction of apical periodontitis increased TG levels significantly, from 63.1 ± 11.4 mg dL-1 in group C to 88.2 ± 7.9 mg dL-1 in the AP group (P < 0.05). The induction of AP was associated with a trend for higher TC and LDL-C levels in atherosclerotic animals (P > 0.05); however, it only significantly increased TG levels, from 93.2 ± 18.0 mg dL-1 in AT group to 121.9 ± 14.5 mg dL-1 in the AP + AT group (P < 0.05). Animals in the AP + AT group had a 36.5% increase in the thickness of the carotid intima tunic when compared with the AT group (P < 0.05). The intensity of the inflammatory infiltrate was significantly larger in the AP + AT group when compared with AP group (P < 0.05). The AP + AT group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 206.4 ± 56.3 × 104 µm2 , compared with 151.4 ± 49.1 × 104 µm2 in the AP group (P < 0.05). CONCLUSION: Apical periodontitis influenced triglyceride levels, increasing them even in the absence of atherosclerosis, and influenced the increase in the thickness of the carotid artery intima tunic in the presence of atherosclerosis. Atherosclerosis intensified the inflammatory reaction and increased bone resorption in periapical lesions.

Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study.

BACKGROUND: Little is known about the risk and predictors of autoimmune diseases in children and adults. OBJECTIVE: To determine the prevalence, predictors, and excess costs of autoimmune disease in atopic dermatitis (AD) patients. METHODS: Cross-sectional study of the 2002-2012 National Inpatient Sample, which includes a ∼20% sample of all US hospitalizations (n = 87,053,155 adults and children). RESULTS: The prevalence of autoimmune disease was higher in adults with AD (7.9%, 95% confidence interval [95% CI] 7.3-8.5%) than without AD (5.7%, 95% CI 5.7%-5.8%) and higher in children with AD (2.0%, 95% CI 1.7%-2.3%) than without AD (1.0%, 95% CI 0.9%-1.1%). In multivariable logistic regression models controlling for sociodemographics, adult (adjusted odds ratio 1.45, 95% CI 1.32-1.58) and pediatric (adjusted odds ratio 2.08, 95% CI 1.73-2.50) AD were associated with any autoimmune disorder. In particular, AD was associated with 18 of 32 autoimmune disorders examined in adults and 13 of 24 examined in children, including disorders of the skin, endocrine, gastrointestinal, hematologic, and musculoskeletal systems. AD patients hospitalized with any autoimmune disorder had a higher cost of inpatient care, with $2.5-$50 million excess annual costs. CONCLUSIONS: Adults and children with AD had increased cutaneous and extracutaneous autoimmune disorders, which were associated with a considerable cost burden.

Dental imaging of trabecular bone structure for systemic disorder screening: A systematic review.

The purpose of this systematic review was to evaluate the potential use of dental imaging assessment of trabecular bone structure in the maxillomandibular complex as an adjuvant screening tool to identify systemic disorders. Five electronic databases and grey literature were searched. Studies were included if they investigated subjects with altered trabecular bone determined by dental radiographs. The QUADAS-2 assessed the risk of bias (RoB) among the studies, while the GRADE determined the strength of evidence. A total of 14 studies that included 1,466 individuals were considered eligible for the qualitative analysis. All studies presented an overall low RoB and low concern regarding applicability. Systemic disorders such as osteoporosis, osteogenesis imperfecta, diabetes, and primary hyperparathyroidism, with their respective control groups, were analyzed among the included studies. Osteoporosis was the condition presenting the most significant results, and 72% of the studies detected changes in the maxillomandibular trabecular bone structure. Studies exploring diabetic edentulous patients found less dense trabecular bone pattern (p < 0.05). In summary, periapical and panoramic radiographs, computed tomography, and cone beam computed tomography imaging could be considered useful for the assessment of the mandibular trabecular bone structure of patients affected by osteoporosis and patients with diabetes.

Gut microbiome-based medical methodologies for early-stage disease prevention.

Recent advancements highlight the important role of gut microbiome in human health. However, a variety of endogenous and exogenous factors, such as genes, foods, drugs, environmental pollutions, oxidative stress, etc., may interfere with the gut microbiome in vivo and increase risks of digestive system diseases, cardiovascular diseases, neurological diseases, obesity, diabetes, cancers, and so on. Abundant discoveries listed in this work support that changes in the composition of the gut microbiome may be potentially used as sensitive early-stage diagnostic biomarkers and that the gut microbiome could be a promising therapeutic target for systemic prevention of multiple human diseases. Interestingly, the microbial culturomics revolution makes it possible to identify much more species and several new species in the gut microbiome. Several innovative articles published by Science and Nature in 2016 further put forward the feasibility of these perspectives, lay grounds for establishing standardized human gut microbiome compositions, and are particularly important for monitoring dysbiosis of the gut microbiome and for precisely reshaping a dysfunctional gut microbiome. Hypothetically, keeping and reconstructing an optimized gut microbiome would be essential to prevent the occurrence of various human diseases. Hence, these advancements have impressive clinical implications for predicting abnormal healthy status of human beings and for preventing the initiation of systemic disorders at an early stage.

Dental Implant Placement in Medically Compromised Patients: A Literature Review.

As a discipline of dentistry, oral implantology deals with the diagnosis, design, insertion, restoration, and/or management of alloplastic or autogenous oral structures for the purpose of regaining contour, function, aesthetics, and speech in a partially or completely edentulous patient. The present review aims to provide the currently available knowledge about the impact of certain systemic disorders and the usage of some medications on the survival rate of dental implant therapy and to highlight the importance of patient management under these conditions. Diabetes, osteoporosis, cardiovascular diseases, and the intake of some medications can increase the risk of the failure of a dental implant. Even though there are relatively few medical contraindications to dental implant treatment, certain conditions may increase the risk of failure or complications.

Toward Digital Periodontal Health: Recent Advances and Future Perspectives.

Periodontal diseases, ranging from gingivitis to periodontitis, are prevalent oral diseases affecting over 50% of the global population. These diseases arise from infections and inflammation of the gums and supporting bones, significantly impacting oral health. The established link between periodontal diseases and systemic diseases, such as cardiovascular diseases, underscores their importance as a public health concern. Consequently, the early detection and prevention of periodontal diseases have become critical objectives in healthcare, particularly through the integration of advanced artificial intelligence (AI) technologies. This paper aims to bridge the gap between clinical practices and cutting-edge technologies by providing a comprehensive review of current research. We examine the identification of causative factors, disease progression, and the role of AI in enhancing early detection and treatment. Our goal is to underscore the importance of early intervention in improving patient outcomes and to stimulate further interest among researchers, bioengineers, and AI specialists in the ongoing exploration of AI applications in periodontal disease diagnosis.

Association of vitiligo with multiple cutaneous and extra-cutaneous autoimmune diseases: a nationwide cross-sectional study.

Previous studies found conflicting results about associations of vitiligo with different autoimmune diseases. To evaluate associations of vitiligo with multiple autoimmune diseases. A cross-sectional study representative of 612,084,148 US patients from the Nationwide Emergency Department Sample (NEDS) 2015-2019 was performed. Vitiligo and autoimmune diseases were identified using International Classification of Diseases-10 codes. The most frequent autoimmune disorders in patients with vitiligo were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, Addison's disease, and systemic sclerosis (SSc). Vitiligo was associated with any autoimmune disorder (adjusted odds ratio [95% confidence interval] 1.45 [1.32-1.58]). Cutaneous disorders with largest effect-sizes were alopecia areata (186.22 [115.31-300.72]) and SSc (32.13 [25.28-40.82]). Non-cutaneous comorbidities with largest effect-sizes were primary sclerosing cholangitis (43.12 [18.98-97.99]), pernicious anemia (41.26 [31.66-53.78]), Addison's disease (33.85 [26.68-42.9]), and autoimmune thyroiditis (31.65 [26.34-38.02]). Vitiligo is associated with multiple cutaneous and non-cutaneous autoimmune diseases, especially in females and older age.

The future of dry powder inhaled therapy: Promising or discouraging for systemic disorders?

Dry powder inhalation therapy has been shown to be an effective method for treating respiratory diseases like asthma, Chronic Obstructive Pulmonary Diseases and Cystic Fibrosis. It has also been widely accepted and used in clinical practices. Such success has led to great interest in inhaled therapy on treating systemic diseases in the past two decades. The current coronavirus (COVID-19) pandemic also has increased such interest and is triggering more potential applications of dry powder inhalation therapy in vaccines and antivirus drugs. Would the inhaled dry powder therapy on systemic disorders be as encouraging as expected? This paper reviews the marketed and in-development dry powder inhaler (DPI) products on the treatment of systemic diseases, their status in clinical trials, as well as the potential for COVID-19 treatment. The advancements and unmet problems on DPI systems are also summarized. With countless attempts behind and more challenges ahead, it is believed that the dry powder inhaled therapy for the treatment of systemic disorders still holds great potential and promise.

Co-infection associated with SARS-CoV-2 and their management.

SARS-CoV-2 was discovered in Wuhan, China and quickly spread throughout the world. This deadly virus moved from person to person, resulting in severe pneumonia, fever, chills and hypoxia. Patients are still experiencing problems after recovering from COVID-19. This review covers COVID-19 and associated issues following recovery from COVID-19, as well as multiorgan damage risk factors and treatment techniques. Several unusual illnesses, including mucormycosis, white fungus infection, happy hypoxia and other systemic abnormalities, have been reported in recovered individuals. In children, multisystem inflammatory syndrome with COVID-19 (MIS-C) is identified. The reasons for this might include uncontrollable steroid usage, reduced immunity, uncontrollable diabetes mellitus and inadequate care following COVID-19 recovery.

COVID-19 infection has reported in the development several other infections and co-morbidity in patients. The present review discusses risk and management strategies in patients suffeting from co-infections caused by COVID-19 infection.

Biological Biomarkers in Respiratory Diseases. / Biomarcadores biológicos en las enfermedades respiratorias.

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area.

Arrhythmias and Conduction Disturbances in Autoimmune Rheumatic Disorders.

Rhythm and conduction disturbances and sudden cardiac death are important manifestations of cardiac involvement in autoimmune rheumatic diseases (ARD), which have a serious impact on morbidity and mortality. While the underlying arrhythmogenic mechanisms are multifactorial, myocardial fibrosis plays a pivotal role. It accounts for a substantial portion of cardiac mortality and may manifest as atrial and ventricular arrhythmias, conduction system abnormalities, biventricular cardiac failure or sudden death. In patients with ARD, myocardial fibrosis is considered to be the hallmark of cardiac involvement as a result of inflammatory process or to coronary artery occlusive disease. Myocardial fibrosis constitutes the pathological substrates for reentrant circuits. The presence of supraventricular extra systoles, tachyarrhythmias, ventricular activity and conduction disturbances are not uncommon in patients with ARDs, more often in systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, inflammatory muscle disorders and anti-neutrophil cytoplasm antibody-associated vasculitis. In this review, the type, the relative prevalence and the underlying mechanisms of rhythm and conduction disturbances in the emerging field of cardiorheumatology are provided.

Prevalence and Risk Factors Associated with the Occurrence of Autoimmune Diseases in Patients with Alopecia Areata.

BACKGROUND: Increased rates of autoimmune diseases (ADs) have been reported in association with alopecia areata (AA); however, the risk factors for coexisting ADs in AA patients have been poorly investigated. OBJECTIVE: To evaluate the prevalence and factors associated with AD comorbidities in patients with AA. METHODS: This case-control study included patients diagnosed with AA between January 2000 and March 2020. Individuals with AA, both with and without concomitant ADs, were statistically compared. Variables significantly associated with coexisting ADs were identified using univariate and multivariate logistic regression analyses. Multinomial logistic regression analysis was performed to identify the specific risk factors for each concomitant AD. RESULTS: Among the 615 patients with AA, comorbid ADs were found in 76 (12.4%). Autoimmune thyroid disease (AITD) exhibited the highest frequency (n = 42, 6.8%), followed by vitiligo (n = 15, 2.4%), and systemic lupus erythematosus (SLE) (n = 12, 2.0%). Logistic regression analyses revealed that female sex (odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.24-4.82; P = 0.011), nail abnormalities (OR = 2.49, 95% CI = 1.14-5.46; P = 0.023), and atopic diseases (OR = 1.98, 95% CI = 1.09-2.43; P < 0.001) were significantly associated with coexisting ADs. Regarding each concomitant AD, nail abnormalities were an associated factor for AITD (OR = 4.65, 95% CI = 1.96-7.24; P = 0.01), whereas coexisting atopic diseases were demonstrated as a predictor of vitiligo (OR = 2.48, 95% CI = 1.43-4.58; P = 0.02). Female sex (OR = 1.61, 95% CI = 1.18-4.27; P = 0.04) and family history of AD (OR = 1.85, 95% CI = 1.26-4.19; P = 0.03) were predictors of SLE. CONCLUSION: This study suggests that female AA patients with nail abnormalities and atopic diseases have increased rates of AD comorbidities. A thorough review of systems for associated factors can help physicians screen for concomitant ADs.

Effect of Cigarette Smoke on Gut Microbiota: State of Knowledge.

Cigarette smoke is a representative source of toxic chemical exposures to humans, and the adverse consequences of cigarette smoking are mediated by its effect on both neuronal and immune-inflammatory systems. Cigarette smoking also is a major risk factor for intestinal disorders, such as Crohn's disease and peptic ulcer. On the other hand, cigarette smoking is protective against developing ulcerative colitis. The effects of cigarette smoking on intestinal disorders include changes in intestinal irrigation and microbiome, increases in permeability of the mucosa, and impaired mucosal immune responses. However, the underlying mechanism linking cigarette smoking with intestinal microbiota dysbiosis is largely unknown. In this communication, we first review the current knowledge about the mechanistic interaction between cigarette smoke and intestinal microbiota dysbiosis, which include the likely actions of nicotine, aldehydes, polycyclic aromatic hydrocarbons, heavy metals, volatile organic compounds and toxic gases, and then reveal the potential mechanisms of the lung-gut cross talk and skin-gut cross talk in regulating the balance of intestinal microbiota and the interrelation of intestinal microbiota dysbiosis and systemic disorders.

CNS involvement in systemic vasculitides.

Both the CNS and the PNS can be involved in almost all of the vasculitides - including the primary systemic vasculitic disorders, such as microscopic polyangiitis and polyarteritis nodosa, and in non-vasculitic systemic disorders, such as systemic lupus erythematosis and sarcoidosis. The latter diseases also include infections and toxininduced disorders - particularly drugs of abuse such as cocaine and amphetamines. Here we will summarise the spectrum of these disorders as they affect the CNS, concentrating in particular on their distinguishing clinical and investigational features.

Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine.

Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies-all exerted system's enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a "sick eye in a sick body" makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles.

Clinical characteristics and prognosis of acquired perforating dermatosis: A case report.

Acquired perforating dermatosis (APD) is an uncommon skin disease characterized by umbilicated hyperkeratotic lesions, and involves the transepidermal elimination of dermal components, including collagen and elastic fibers. The disease can affect patients with systemic disorders, especially those with chronic renal failure or diabetes mellitus. The current paper described four cases of patients with APD and investigated the clinical characteristics and prognosis of APD, as well as its possible link with systemic disorders. In each of the four cases, the patient had systemic disorders before the onset of APD, three had concomitant renal and thyroid disorders and one had hepatocirrhosis secondary to chronic hepatitis C. The results of the present study showed that APD occurred after the transient worsening of the original systemic disease. Furthermore, it was revealed that dermatosis symptoms were alleviated upon remission of the original systemic disorder, without specific dermatological treatment. Dermatosis symptoms improved in all four patients, indicating that the management of the associated systematic diseases was essential for the successful clinical outcomes of APD.