Novel Vehicles For Drug Delivery in Atopic Dermatitis: A Narrative Review.

INTRODUCTION: Atopic dermatitis (AD) causes dry and itchy skin and inflammation that severely impairs the quality of life of affected children and adults. While topical glucocorticosteroid application is typically the first-line treatment of choice, steroid treatment is associated with side effects and, increasingly, patient concerns about prolonged use. Novel drugs and drug delivery vehicles are required for patients with AD. OBJECTIVES: To summarize the current literature on novel topical agents for atopic dermatitis and novel delivery vehicles. METHODS: A literature search was conducted, and a narrative review was compiled to summarize recent evidence. RESULTS: Novel topical drugs approved or in late-phase clinical trials for the treatment of AD include the Janus kinase inhibitor ruxolitinib, the phosphodiesterase-4 inhibitors crisaborole, and roflumilast, and the aryl hydrocarbon receptor activator tapinarof. While current topical drugs for AD are delivered via creams, ointments, gels, and related vehicles, novel delivery approaches such as electrospun patches, sprays, liposomes, nanoparticles, and lasers are being developed to enhance transdermal delivery, reduce side effects, and increase treatment adherence. CONCLUSIONS: Topical application of creams or ointments is currently the predominant vehicle for the delivery of atopic dermatitis drugs. In vitro studies on novel vehicles show promising results to overcome the issues associated with topical delivery. Still, these findings have to be corroborated by controlled studies with human patients in the future.

Efficacy and safety of combinational therapy using topical minoxidil and microneedling for the treatment of androgenetic alopecia: a systematic review and meta-analysis.

Androgenetic alopecia is a widespread condition that is the most common type of hair loss affecting approximately 58% and 40% of men and women by the age of 50, respectively. Patients have been known to experience severe distress due to androgenetic alopecia, including anxiety, low self-esteem, and depression. The objective of this study was to conduct a systematic review and meta-analysis to determine the efficacy of combination therapy using topical minoxidil and microneedling compared to topical minoxidil alone. This systematic review of randomized controlled trials was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. The literature search was performed using Scopus, Cochrane, Embase, and the National Institutes of Health's United States National Library of Medicine from inception through January 20, 2023. Randomized controlled trials examining the efficacy of combinational therapy and monotherapy using microneedling and minoxidil on patients with clinically diagnosed androgenetic alopecia were included after screening titles, abstracts, and full texts. Two independent reviewers selected studies, extracted data, and appraised the risk of bias using the Cochrane risk of bias assessment tool. Ten randomized controlled trials, including 466 patients, were selected for this review and eight studies were ultimately included in the meta-analysis. All eight studies displayed a statistically significant increase in total hair count [standard mean difference (SMD) 1.76; 95% CI 1.26-2.26; P < 0.00001]; however, the evidence did not support a statistically significant increase in hair diameter (SMD 0.82; 95% CI - 0.01 to 1.65; P = 0.05). No scarring nor serious adverse events were reported in any of the studies. The findings of this meta-analysis strongly support the utilization of a multimodal therapeutic approach of minoxidil and microneedling for hair growth in patients with androgenetic alopecia. However, variations in factors such as rating scale measurements, microneedling methods, and areas of treatment may have resulted in confounding. Further randomized controlled, large-sample trials employing rigorous methodologies are needed to gain a more comprehensive understanding regarding treatment efficacy, namely the impact of combinational therapy on hair diameter.Clinical trial registrations This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and is registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023391164) and the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) database (INPLASY202310031).

Unmasking Racial Disparity in the Diagnosis and Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, profoundly incapacitating disease predominantly affecting the apocrine gland-rich areas of the human body. Although it affects 0.05% to 4% of the general population, there exists a significant racial disparity, with people of color, particularly Black individuals, experiencing a notably higher prevalence. Despite this disparity, the current literature lacks comprehensive analyses of HS concerning race and ethnicity, revealing a systemic blind spot in understanding and addressing the disease's racially disproportionate impacts. In this commentary, we aim to shed light on these racial disparities, focusing specifically on the stark inequities related to the timely diagnosis and subsequent dermatological care of HS in the United States. This commentary explores the racial bias in HS prevalence, severity, diagnostic delay, access to specialized care, and underrepresentation in clinical trials. By emphasizing the urgent need to address these disparities, we seek to foster an inclusive dialogue and drive proactive efforts toward achieving equitable care and research representation for all populations affected by this debilitating condition. Through this discussion, we aim to pave the way for a healthcare landscape that acknowledges and addresses the racial disparities inherent in HS, ensuring that advancements in the management of the disease cater to the needs of all populations, irrespective of their racial or ethnic background.

Cutaneous Manifestations of Malaria and Their Prognostic Windows: A Narrative Review.

Malaria is a vector-borne tropical infection caused by protozoa of the genus Plasmodium and is transmitted by the bite of an infected Anopheles mosquito. The disease is commonly characterized by fever, edema, thrombocytopenia, hypoglycemia, anemia, and myalgias; however, the infection's cutaneous presentations are not commonly emphasized and tend to be overlooked. A literature search was conducted that focused on the various skin pathologies that malaria patients have been noted to present with using case reports and currently available literature. We describe the various skin manifestations associated with malaria, such as purpura fulminans, febrile urticaria, cutaneous leishmaniasis co-infections, urticaria infectiosum, vivax-induced severe thrombocytopenia petechiae, acral skin necrosis, and reticulated erythema, and how each of these skin manifestations may provide insight into the patient's prognosis. Documentation and vigilance regarding these cutaneous manifestations must be emphasized as they may lead to better patient outcomes and a stronger understanding of the patient's underlying malaria.

Non-invasive skin measurement methods and diagnostics for vitiligo: a systematic review.

Vitiligo is a multifaceted autoimmune depigmenting disorder affecting around 0.5 to 2.0% of individuals globally. Standardizing diagnosis and therapy tracking can be arduous, as numerous clinical evaluation methods are subject to interobserver variability and may not be validated. Therefore, there is a need for diagnostic tools that are objective, dependable, and preferably non-invasive. Aims: This systematic review provides a comprehensive overview of the non-invasive objective skin measurement methods that are currently used to evaluate the diagnosis, severity, and progression of vitiligo, as well as the advantages and limitations of each technique. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used for the systematic review. Scopus, Embase, Cochrane Library, and Web of Science databases were comprehensively searched for non-invasive imaging and biophysical skin measuring methods to diagnose, evaluate the severity of, or monitor the effects of vitiligo treatment. The risk of bias in included articles was assessed using the QUADAS-2 quality assessment scale. Results: An extensive literature search resulted in 64 studies for analysis, describing eight imaging techniques (reflectance confocal microscopy, computer-aided imaging analysis, optical coherence tomography, infrared photography, third-harmonic generation microscopy, multiphoton microscopy, ultraviolet light photography, and visible light/digital photograph), and three biophysical approaches (dermoscopy, colorimetry, spectrometry) used in diagnosing and assessing vitiligo. Pertinent information about functionality, mechanisms of action, sensitivity, and specificity was obtained for all studies, and insights into the strengths and limitations of each diagnostic technique were addressed. Methodological study quality was adequate; however, statistical analysis was not achievable because of the variety of methods evaluated and the non-standardized reporting of diagnostic accuracy results. Conclusions: The results of this systematic review can enhance clinical practice and research by providing a comprehensive overview of the spectrum of non-invasive imaging and biophysical techniques in vitiligo assessment. Studies with larger sample sizes and sound methodology are required to develop verified methods for use in future practice and research. Systematic review registration: (PROSPERO) database, (CRD42023395996).

Acceptance, availability, and feasibility of RTS, S/AS01 malaria vaccine: A review.

INTRODUCTION: In malaria-stricken regions, malaria continues to be one of the primary causes of mortality for children. The number of malaria-related fatalities has drastically decreased because of artemisinin-based pharmacological regimens. METHODS: Two independent researchers did a comprehensive literature search using PubMed/MEDLINE and Google Scholar from its inception to September 2022. RESULTS: After evaluating RTS, S/AS01 for its safety, effectiveness, and feasibility, the European Medicines Agency (EMA) issued a favorable conclusion. It was suggested that the RTS, S malaria vaccine be used extensively by the World Health Organization on October 6, 2021. The successful pilot program testing the malaria vaccine in Ghana, Kenya, and Malawi served as the basis for this proposal. CONCLUSION: Several challenges need to be addressed to ensure the success of vaccination programs. From the acceptability perspective, issues such as inadequate community engagement, concerns about side effects, and issues with the delivery and quality of healthcare services can affect the acceptance of the vaccine. From the feasibility standpoint, factors such as lack of transportation or long distances to healthcare facilities and the perception of completion of the vaccination calendar can affect the feasibility of the vaccine. Lastly, the availability of the vaccine is also a major concern as it may not be readily available to meet the demands.

Muscular Weakness with Calcinosis Cutis_A Case of Juvenile Dermatomyositis in a South Asian Male.

Background: Juvenile dermatomyositis (JDM) is an autoimmune connective tissue disorder characterized by an inflammation of proximal muscles of both upper and lower limbs in children below the age of 18 years. The condition mainly involves the proximal muscles and skin but extra-muscular involvement such as the gastrointestinal tract, lungs, and heart are also common. Case presentation: We present a case of a 12-year-old south Asian male who developed weakness and muscular pain in all 4 extremities at 3 years of age. The condition gradually worsened recently, and the patient developed tender ulcerated skin nodules. Power in all 4 limbs was decreased and the patient was not able to perform his routine work such as combing of hair, closing a shirt button, and walking. Laboratory investigations revealed raised total leukocyte count (TLC) and erythrocyte sedimentation rate (ESR) and biopsy of the proximal muscles and skin lesions showed focal mild necrotic infiltrate involving nonnecrotic muscle fibers and calcinosis cutis respectively. A diagnosis of JDM was made and the patient was started on immunosuppressive therapy (steroids) and diltiazem. Conclusion: JDM shares clinical features with other autoimmune, genetic, and inflammatory conditions. Proper history, thorough clinical examination, and laboratory workup is needed to rule out other masquerading conditions. This case report also highlighted the importance of diltiazem in the treatment of calcinosis cutis which is more commonly seen in patients with dermatomyositis.

Effectiveness of laser and topical tranexamic acid combination therapy in melasma: An updated systematic review and meta-analysis of randomized controlled trials.

Melasma is a chronic relapsing skin condition. Laser therapy is a new advancement in treatment. Whether the topical application of tranexamic acid (TXA) increases the efficacy of laser therapy in melasma is still under debate. With recent studies yielding different results, it was imperative to compile all the available literature systematically. This meta-analysis investigates the effectiveness of a combination therapy of laser plus TXA acid for treating melasma. PubMed/MEDLINE, Cochrane Central, Google Scholar, Scopus, and the International Clinical Trials registry were systematically searched for article retrieval. Screening per PRISMA guidelines was undertaken by two independent reviewers using the Covidance database. Melasma area of severity index (MASI)/modified MASI was used as the clinical improvement outcomes. A total of nine studies that described the combined use of topical tranexamic acid with laser therapy were included for meta-analysis. These studies employed various types of lasers along with topical TXA. The results showed that the combination of both laser therapy and topical TXA significantly decreased the MASI score (P < 0.0001). Subgroup analyses revealed that fractional CO2 laser among the laser types and monthly laser plus twice daily topical TXA were most effective in decreasing the MASI/mMASI score. The meta-analysis found that combining topical tranexamic acid and laser therapy is an effective and safer treatment option for treatment-resistant melasma. Furthermore, monthly fractional CO2 laser and daily application of topical tranexamic acid showed high effectiveness and safety.

Diagnostic Dilemma of ANA-negative Pediatric Systemic Lupus Erythematosus in a South Asian Female.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organs with different degrees of severity. SLE is typically diagnosed based on the presence of antinuclear antibodies (ANA) in the serum. However, seronegative SLE is rare and is diagnosed by clinicians when the patient's ANA is negative but fulfills other diagnostic criteria. Case report: We report a case of a 15-year-old South Asian female with SLE who had negative antinuclear antibodies yet displayed the typical clinical presentations of photosensitive maculopapular rash, joint pain, alopecia, anemia, and thrombocytopenia. Clinical evaluations in conjunction with lab results were used to establish a diagnosis of ANA-negative SLE. Conclusion: ANA positivity is an entry criterion for SLE; rarely, cases of ANA-negative SLE may present. A typical clinical presentation may help determine the diagnosis in such a scenario. However, still, the physician should rule out immunodeficiency and other systemic illnesses before reaching a diagnosis of ANA-negative pediatric SLE.

Blue Rubber Bleb Nevus Syndrome Presenting as Anemia, Hemorrhage, and Hemangiomas: A Rare Case Report.

Background: Blue Rubber Bleb Nevus syndrome (BRBNS) is a rare disorder, that results in congenital cutaneous hemangiomas of the skin and gastrointestinal tract. Although asymptomatic, the nevi present as soft, non-mobile, dark blue, compressible papules. Clinically it presents as iron deficiency anemia due to occult gastrointestinal bleeding. Case presentation: A 22-year-old female patient presented with complaints of shortness of breath, fatigue, and palpitation for 2 months. On examination, she had a pale effect and widespread hemangiomas on her lips, hands, and feet. Laboratory results revealed iron deficiency anemia with hemoglobin (Hb) of 2.1 gm/dl and histopathology results of the hemangioma specimen showed angiokeratomas. Based on clinical manifestations and laboratory results, the patient was diagnosed with a case of BRBNS. The patient was transfused with red cell concentrate her symptoms improved but on the first follow-up visit her Hb again dropped to 8.6 mg/dl. Conclusion: A high suspicion of BRBNS diagnosis should be considered if a patient presents with iron deficiency anemia and multiple cutaneous hemangiomas. Further screening should be done to explore internal bleeding and hemangiomas.

The Intersection Between Malaria Treatment and Chemoprophylaxis and Their Potential Adverse Dermatologic Manifestations: A Narrative Review.

Malaria is a life-threatening parasitic disease caused by various forms of the protozoa Plasmodium and is transmitted by the female Anopheles mosquito. The parasitic infection is endemic in 90 countries, with approximately 500 million cases reported annually and an estimated annual mortality of 1.5-2.7 million individuals. Historically, the use of antimalarial drugs has been promising for the chemoprophylaxis and treatment of malaria, mitigating the annual mortality rate. Notably, these antimalarial drugs have been associated with various adverse effects, including gastrointestinal upset and headaches. However, the adverse cutaneous manifestations these antimalarial drugs may lead to are poorly documented and understood. We aim to describe the lesser-studied adverse cutaneous pathologies of malaria treatment to better educate physicians on the proper treatment of their patients. Our narrative review describes the skin manifestations associated with specific antimalarial treatments and their associated prognoses and treatments. The cutaneous pathologies discussed include aquagenic pruritus (AP), palmoplantar exfoliation, Steven-Johnson syndrome, toxic epidermal necrolysis, cutaneous vasculitis, psoriasis, ecchymosis, and tropical lichenoid dermatitis. Further studies and vigilant documentation of the cutaneous adverse events of antimalarial drugs need to be performed and emphasized to prevent potential life-threatening adverse outcomes.

An Erythrodermic Psoriasis Flare-Up With Staphylococcus Bacteremia Secondary to COVID-19 Infection: A Case Report.

Erythrodermic psoriasis (EP) is an autoimmune condition commonly manifested as cutaneous lesions, such as well-demarcated, erythematous, scaly plaques, notably on the extensor surfaces but sometimes present on the scalp, palms, and soles. Various triggering events are known to initiate flare-ups of previously well-controlled/dormant EP. In recent literature, the association of acutely exacerbated EP after symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been well-described. Here, we present a case of EP with increased flaking and desquamation of the skin of the whole body (most notably on the palms and soles) after three weeks of symptomatic SARS-CoV-2 infection without any other evident trigger. We aim to describe the symptoms as well as the proper management of a patient afflicted with erythrodermic psoriasis in hopes of aiding future clinicians in the prompt diagnosis and treatment of such a patient.

Snakebite Induced Cerebral Venous Sinus Thrombosis: A Case Report.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare but highly fatal neurological condition mostly caused by prothrombotic conditions like antiphospholipid syndrome, factor V Leiden, and G20210A prothrombin polymorphism. Snake bites are a rare cause of cerebral venous sinus thrombosis that must be recognized and treated promptly to improve survival. Case presentation: We present a case of a 25-year-old male who developed headaches and seizures following a Viper snake bite. The diagnosis was made based on a magnetic resonance venogram (MRV) showing transverse sinus thrombosis with sigmoid sinus stenosis. Initially, the patient was treated with antivenom and supportive treatment for disseminated intravascular coagulation (DIC). After the diagnosis of CVST, the patient was treated with rivaroxaban and levetiracetam. The patient improved within 1 week of treatment and was advised to follow up in 3 months. Conclusion: A high index of suspicion for cerebral venous sinus thrombosis is required if the patient presents with headaches, seizures, or abnormal vision following a snake bite. Early diagnosis and management can prevent further neurological damage.

Non-syndromic Intellectual Disability: An Experimental In-Depth Exploration of Inheritance Pattern, Phenotypic Presentation, and Genomic Composition.

Background Intellectual disability (ID), also termed mental retardation (MR), is a neurodevelopmental disorder characterized by an intelligence quotient (IQ) of 70 or below and a deficit in at least two behaviors associated with adaptive functioning. The condition is further classified into syndromic intellectual disability (S-ID) and non-syndromic intellectual disability (NS-ID). This study highlights the genes associated with NS-ID. Objectives A genetic study was performed on two Pakistani families to know the inheritance patterns, clinical phenotypes, and molecular genetics of affected individuals with NS-ID. Methodology Samples were collected from two families: families A and B. All affected individuals in both families were diagnosed by a neurologist. Written informed consent was taken from the affected individuals and guardians before collecting the data and sample. Family A belongs to the Swabi District of Pakistan having four affected individuals, out of whom three were male and one was female. Family B also belongs to the Swabi District of Pakistan having two affected individuals, out of whom one was male and one was female. A total of 10 candidate genes were selected and were further screened by microarray analysis. Results In family A, this analysis identified a region of 9.6 Mb on chromosome 17q11.2-q12 between the single nucleotide polymorphisms (SNPs) rs953527 and rs2680398. The region was genotyped using microsatellite markers to confirm the haplotypes in all family members. Based on the phenotype-genotype relationship, 10 possible candidate genes were selected out of more than 140 genes in this critical region of 9.6 Mb. In family B, homozygosity mapping through microarray identified four homozygous areas of affected individuals: two (27,324,822-59,122,062 and 96,423,252123,656,241) on chromosome 8, one (14,785,224-19,722,760) on chromosome 9, and one (126173647-126215644) on chromosome 11. Conclusion An autosomal recessive pattern was found in the pedigrees of both families A and B. Phenotypically affected individuals showed IQ levels below 70. Three genes, CDK5R1, OMG, and EV12A, were found on chromosome 17q11.2-q12 region of affected individuals in family A with high expression in the frontal cortex of the brain, hippocampus, and spinal cord, respectively. Other regions on chromosomes 8, 9, and 11 as evident from the affected individuals in family B can also contribute to the non-syndromic autosomal recessive intellectual disability (NS-ARID). Further research is needed to find the association of these genes with intelligence and other neuropsychiatric conditions.

Clinical manifestations of Apert syndrome.

Apert syndrome presents similarly to the one we presented in this image, and a genetic study is used for confirmation. This image shows the typical findings of physical examination, so that if this appears in the outpatient department, the diagnosis of Apert syndrome should be assumed.

The Diagnostic Dilemma of Splenic Non-Hodgkin's Lymphoma and Splenic Abscess: A Narrative Review.

Non-Hodgkin's lymphoma (NHL) is a lymphoproliferative disorder that principally displays lymph node involvement but can also spread to extranodal sites such as the spleen. Primary splenic NHL arises in the spleen and, due to its atypical presentation, can sometimes present similarly to other splenic conditions. This review aims to highlight how primary splenic NHL can be effectively differentiated from other splenic conditions, such as splenic abscesses. PubMed, MEDLINE, Scopus, Google, and Google Scholar were used to identify articles mainly focused on splenic non-Hodgkin's lymphoma and splenic abscess. The search was limited to articles published from January 2005 to November 2022. Of the 229 total articles amassed, only 34 were selected and narratively reviewed. From a thorough review of the current literature, it is evident that splenic NHL displays a similar clinical picture to other splenic conditions, namely splenic abscesses. One cannot easily differentiate between the two conditions, both clinically and via diagnostic imaging. Lymphadenopathy, a hallmark sign of nodal NHL, may or may not be present in splenic NHL. Ultimately, splenectomy with biopsy and immunohistochemical staining (IHC) may be required to confirm the diagnosis. In cases of suspected splenic NHL or splenic abscess with little-to-no symptomatic improvement after medication administration, splenectomy followed by histopathological examination may be required for a definitive diagnosis and proper treatment.

Giving Rest to the Restless Leg: A Case Report of How Self-Education Prepending Web-Based Interventions Can Ameliorate Restless Leg Syndrome.

Restless leg syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move one's leg sporadically. The pathogenesis of RLS, also known as Willis Ekborn disease, is not fully understood; however, scientists note a complex interplay between multiple neuronal pathway-related genes with endogenous and exogenous factors. We report a case of a previously healthy 27-year-old man complaining of a continuous urge to move his right leg, notably at night. Laboratory evaluation proved negative for secondary causes of RLS; hence the condition was labeled as "primary idiopathic." The patient was started on appropriate pharmacotherapy and was advised to self-educate regarding his ailment. The patient began internet-based self-education and displayed excellent improvements on the International Restless Leg Syndrome Scale (IRLS). Mental exercises, such as self-education using web-based intervention and pharmacotherapy, could alleviate factors in patients with primary idiopathic RLS. Further research is needed to clarify self-education's role in managing RLS.

An Insight Into the Acceptance and Hesitancy of COVID-19 Vaccines in Pakistan: A Cross-Sectional Survey.

BACKGROUND: COVID-19 vaccines are found to be effective interventions to tackle COVID-19. However, the hesitancy towards its acceptance has been rising in Pakistan. This study highlights the opinion of the general population in Pakistan regarding the acceptance and hesitancy of COVID-19 vaccination. METHODS: A descriptive cross-sectional survey study was conducted among Pakistanis from December 2021 to January 2022. Adult respondents that have and have not received COVID-19 vaccinations were included in this study. Data collection was obtained through questionnaires that assessed acceptance and hesitancy toward COVID-19 vaccines. Statistical analysis was performed using IBM SPSS software version 25 for Windows. RESULTS: We obtained 367 respondents with 333 respondents completing the questionnaire. There were 259 respondents who have been vaccinated. A total of 67.9% of responses agreed that vaccines could control the COVID-19 pandemic. The reasons for not getting vaccination were afraid of adverse effects (48.6%) and COVID-19 vaccines not being tested thoroughly (30.9%). The main reason for vaccine acceptance was awareness about vaccines (23.1%), a belief that vaccines can stop severe COVID-19 disease (16.8%), and self-protection (14.7%). CONCLUSION: Most Pakistanis agreed that vaccines could manage the pandemic. Vaccine acceptance was contributed by the awareness and belief regarding the protective effects of vaccines while vaccine hesitancy was due to the public's doubt about the vaccines' side effects and testing. The Pakistan government should focus on emphasizing knowledge about vaccines, educating the vaccines' adverse effects, and utilizing social media in doing so.

Intracellular C3 Protects Human Airway Epithelial Cells from Stress-associated Cell Death.

The complement system provides host defense against pathogens and environmental stress. C3, the central component of complement, is present in the blood and increases in BAL fluid after injury. We recently discovered that C3 is taken up by certain cell types and cleaved intracellularly to C3a and C3b. C3a is required for CD4+ T-cell survival. These observations made us question whether complement operates at environmental interfaces, particularly in the respiratory tract. We found that airway epithelial cells (AECs, represented by both primary human tracheobronchial cells and BEAS-2B [cell line]) cultured in C3-free media were unique from other cell types in that they contained large intracellular stores of de novo synthesized C3. A fraction of this protein reduced ("storage form") but the remainder did not, consistent with it being pro-C3 ("precursor form"). These two forms of intracellular C3 were absent in CRISPR knockout-induced C3-deficient AECs and decreased with the use of C3 siRNA, indicating endogenous generation. Proinflammatory cytokine exposure increased both stored and secreted forms of C3. Furthermore, AECs took up C3 from exogenous sources, which mitigated stress-associated cell death (e.g., from oxidative stress or starvation). C3 stores were notably increased within AECs in lung tissues from individuals with different end-stage lung diseases. Thus, at-risk cells furnish C3 through biosynthesis and/or uptake to increase locally available C3 during inflammation, while intracellularly, these stores protect against certain inducers of cell death. These results establish the relevance of intracellular C3 to airway epithelial biology and suggest novel pathways for complement-mediated host protection in the airway.