Bone marrow transplantation and bone marrow-derived mesenchymal stem cell therapy in epidermolysis bullosa: A systematic review.

Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life-threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM-MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft-versus-host disease, and renal insufficiency. Allogeneic BMT is a high-risk procedure with possible benefits and adverse events. BM-MSCs revealed favorable outcomes to improve the safety of EB cell-based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment's long-term effects and clarify the risk/benefit ratio of procedure versus conventional therapy.

COVID arm as a common cutaneous manifestation after mRNA-1273 vaccination: a systematic review.

BACKGROUND: By August 2022, CoronaVirus Disease-2019 (COVID-19) had caused 600 million illnesses and 6.5 million fatalities globally. A massive vaccination program is being implemented worldwide to suppress this condition. Several works of literature stated that mRNA COVID-19 vaccination, specifically with the mRNA-1273 vaccine, is followed by clear evidence of the COVID arm effects associated with this vaccine. OBJECTIVE: To analyze the latest evidence of COVID arm as a common effect of mRNA-1273 vaccination with the ultimate goal of improving vaccine counseling to help healthcare professionals and reassure patients. METHODS: A comprehensive search was performed on topics that assess the COVID arm as a cutaneous manifestation following mRNA-1273 vaccination from inception up until July 2022. RESULTS: Eighteen studies with a total of 1129 participants after the first and second dose of mRNA-1273 vaccination reported that most participants had COVID arm following the first dose administration. The characteristics of the patients were a mean age of 43.8 years old, and females represented ≥ 50% in most studies, with a mean onset of 6.9 days after the first dose administration. Symptoms resolved within seven days following the treatment and were harmless. CONCLUSIONS: This study found that the COVID arm condition is most common following the first mRNA-1273 vaccination in the female and middle-aged group. The correlation between demographic variables and COVID arm risk elucidates that the reaction is a type IV allergic skin reaction.

Cutaneous Manifestation in COVID-19: A Lesson Over 2 Years Into the Pandemic.

Cutaneous manifestations related to Coronavirus Disease-19 (COVID-19) have been reported over 2 years since the pandemic began. This research aimed to review articles published in English that describe cutaneous manifestations related to COVID-19/SARS-CoV-2. A data search for case reports, original studies, and review articles from the onset of the current COVID-19 pandemic to December 31, 2022, was performed using PUBMED, Cochrane Library, ResearchGate, and Google search engines. Keywords were "coronavirus", "novel coronavirus 2019", "COVID-19", "SARS-CoV-2", and "2019-nCoV" in combination with "cutaneous", "skin" and "dermatology" The extracted data included authors, region, sex, age, number of participants with skin signs, cutaneous signs, its location, symptoms, extracutaneous/associated symptoms, suspected or confirmed status for COVID-19, timeline, and healing duration. Six authors independently reviewed the abstracts and full-texts to identify publications providing these details concerning cutaneous manifestations related to COVID-19. A total of 139 publications with full text (122 case reports, 10 case series, and 7 review articles) that reported cutaneous manifestations were identified, and reviewed from 5 continents. The most common cutaneous manifestations of COVID-19 were maculopapular, followed by chilblain-like lesion, urticarial, livedoid/necrotic, vesicular, and other/non-descript rashes/skin lesions. After 2 years into the COVID-19 pandemic, we can conclude that there is no pathognomonic cutaneous manifestation of COVID-19, since it can be also found in other viral infections.

Transcriptomic profiling of recessive dystrophic epidermolysis bullosa wounded skin highlights drug repurposing opportunities to improve wound healing.

Chronic wounds present a major disease burden in people with recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering skin disorder caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils at the dermal-epidermal junction. Treatment of RDEB wounds is mostly symptomatic, and there is considerable unmet need in trying to improve and accelerate wound healing. In this study, we defined transcriptomic profiles and gene pathways in RDEB wounds and compared these to intact skin in RDEB and healthy control subjects. We then used a reverse transcriptomics approach to discover drugs or compounds, which might restore RDEB wound profiles towards intact skin. Differential expression analysis identified >2000 differences between RDEB wounds and intact skin, with RDEB wounds displaying aberrant cytokine-cytokine interactions, Toll-like receptor signalling, and JAK-STAT signalling pathways. In-silico prediction for compounds that reverse gene expression signatures highlighted methotrexate as a leading candidate. Overall, this study provides insight into the molecular profiles of RDEB wounds and underscores the possible clinical value of reverse transcriptomics data analysis in RDEB, and the potential of this approach in discovering or repurposing drugs for other diseases.

Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

Generalized epidermolytic ichthyosis with palmoplantar hyperkeratosis.

Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified clinically based on the presence of palmoplantar hyperkeratosis involvement and extent of skin involvement. The diagnosis is made by clinical and histopathological examinations that can be confirmed by genetic testing. We present a 2-year-old girl who presented with erythematous and thick scaling skin. Her condition began at birth as multiple flaccid blisters that would easily break into erosions. There was no history of similar condition nor consanguinity within her family. Skin examination revealed diffuse erythematous skin covered with thick scales and erosion, predominantly on her face, extremities, palms, and soles. The skin histopathology examination showed diffuse parakeratosis with vacuolar and granular degeneration within granular and spinous layers along the epidermis. She was diagnosed with generalized EI with palmoplantar hyperkeratosis based on the clinical and histopathological examinations. Clinical improvement was observed after a one-month treatment with mupirocin cream, sodium bicarbonate bath, and moisturizer after bathing.

Development of polymeric nanoparticle gel prepared with the combination of ionic pre-gelation and polyelectrolyte complexation as a novel drug delivery of timolol maleate.

OBJECTIVE: The purpose of this study was to overcome the undesired systemic absorption of skin topical administration of timolol maleate (TM) by developing the TM nanoparticle gel. METHODS: TM-loaded nanoparticle (TMNP) was prepared by ionic pre-gelation of pectin (PCN) and calcium ions (CI) followed with polyelectrolyte complex using chitosan (CHI). TMNP was characterized by measuring the particle size, polydispersity index, zeta potential, encapsulation efficiency (EE), and the interaction between formula constituents. TM-loaded nanoparticle gel (TMNG) was prepared by using hydroxypropyl methylcellulose (HPMC) and was characterized by measuring the spreadability, pH, viscosity, and drug content. The drug release kinetics were analyzed using DDSolver add-in program. RESULTS: TMNP possessed particle size of 175.2 ± 19.7 nm, polydispersity index of 0.528 ± 0.113, zeta potential of -10.86 ± 0.87 mV, and EE of 27.45 ± 2.34%. The electrostatic interactions between PCN, CI, and CHI that formed the nanoparticles were confirmed by the result of vibrational spectroscopy analysis. TMNG possessed spreadability of 60.80 ± 1.38 cm2, pH of 5.154 ± 0.004, viscosity of 269.07 ± 5.83 cP, and drug content of 107.38 ± 1.77%. TM showed a sustained release manner within 24 h by following Korsmeyer-Peppas kinetical model with non-Fickian release mechanism. CONCLUSION: The prepared nanoparticle gel can be an effective controlled release system of TM that administered topically on the skin surface.

The Role of Moisturizers in Addressing Various Kinds of Dermatitis: A Review.

Moisturizer is a major component of basic daily skin care, particularly in presence of epidermal barrier alteration and reduced epidermal water content. It is an important part of a dermatologist's strategy to maintain skin health as well as treating various dermatoses which co-exist with skin dryness and are linked to impaired skin barrier function, such as in atopic disorders as well as other types of dermatitis. Mastering the knowledge regarding mechanism of action, application, dosage, adverse effects as well as specific clinical usage of moisturizers is a must for a dermatologist in order to support their use, particularly for evidence-based, therapeutic purposes. This review discusses the use of moisturizer both for skin health maintenance as well as a definitive or adjuvant therapy for many kinds of dermatitis.

Topical Timolol Maleate 0.5% for Infantile Hemangioma: Its Effectiveness Compared to Ultrapotent Topical Corticosteroids - A Single-Center Experience of 278 Cases.

BACKGROUND: Infantile hemangioma (IH) may have implications on parental distress and cosmetic disfigurement. To date, ultrapotent corticosteroids are used as a treatment of choice for superficial IH. However, due to their side effects and sometimes lack of IH regression, it is necessary to find alternative topical therapies. Timolol maleate 0.5% solution and gel are nonselective ß-blockers that could inhibit proliferation and trigger regression of IH. OBJECTIVE: To evaluate the efficacy of topical ultrapotent corticosteroids and timolol maleate 0.5% solution and gel for superficial IH. PATIENTS AND METHODS: The study design was prospective. Two hundred and seventy-eight patients diagnosed as having superficial IH were enrolled from the outpatient clinic of the Department of Dermatology and Venereology, Dr. Sardjito Hospital, Yogyakarta, Indonesia, from January 2009 to December 2014. Patients were divided into three groups: A = treated with topical ultrapotent corticosteroid, B = timolol maleate 0.5% solution and C = timolol maleate 0.5% gel. Patients were followed for 6 months to evaluate the lesion. Lesion size was measured from scaled photodocumentation with the software program ImageJ®. RESULTS: There were significant differences in IH size after treatment with timolol maleate 0.5% solution compared with ultrapotent corticosteroids (p < 0.001) and timolol maleate 0.5% gel compared with ultrapotent corticosteroids (p < 0.001). There was no significant difference in IH lesions after treatment with timolol maleate 0.5% solution versus gel (p = 0.744). CONCLUSION: Timolol maleate 0.5% solution and gel were significantly superior to topical ultrapotent corticosteroids in size reduction of superficial IH.

Asian herbal medicine for atopic dermatitis: a systematic review.

Asian herbal medicines have been known for decades, and some have been used to treat atopic dermatitis (AD). This chronic and persistent inflammatory skin condition causes severe morbidity and negatively impacts the quality of life. In numerous trials, traditional Chinese medicines have demonstrated clinical efficacy for AD. However, there is no well-documented summary of the wide variety of Asian herbal medicines used in treating AD. We aimed to systematically summarize the use of Asian herbal medicine in AD. An English-language literature search was performed in three electronic medical databases: PubMed, Cochrane Library, and EBSCOhost using keywords [("atopic dermatitis" OR "atopic eczema") AND ("traditional" OR "herbal")] and limited to references published between January 2015 and December 2022. The literature included newborns, infants, children, adolescents, and adults. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to determine the main criteria. The content and inclusiveness of the search were filtered using relevant terms (MeSH/Emtree), keywords, titles, and abstracts. Thirteen articles (12 randomized clinical trial + 1 clinical trial) reported a variety of herbal medicine compounds to treat AD with various efficacy. Most studies reported significant improvement when comparing the herbal medicine with a placebo, but only 1 study reported substantial improvement of SCORAD compared to corticosteroids. Asian herbal medicines have been studied and may be used as an alternative treatment in treating AD with fewer adverse effects. However, its role did not change the position of standard treatment in treating atopic dermatitis.

A randomised clinical trial study assessing the efficacy of 5% losartan potassium loaded in ethosomal gel to treat human keloids: a trial protocol.

BACKGROUND: Keloid is a skin disorder that results from excessive fibrous tissue growth in the area of the initial trauma. Treating keloids can be challenging since the success of various treatments varies from one study to another. Triamcinolone acetonide injection, a standard treatment, can cause undesirable side effects. Meanwhile, the effectiveness of existing topical therapies for keloids is not always reliable. The pro-inflammatory, pro-proliferative, and pro-fibrotic effects of angiotensin II in human skin contribute to keloid formation. Losartan potassium, an angiotensin II blocker, has the potential to act as an anti-keloid agent. Due to the thicker skin structure of a keloid and ease of application, ethosome gel is chosen as a safe and comfortable carrier for losartan potassium, making it a good choice for treating keloids. METHODS: In this randomised clinical trial, 46 adults with keloids were divided into two treatment groups. One group of 23 participants received 5% losartan potassium loaded in ethosomal gel, while the other group of 23 participants received intralesional injections of 10% triamcinolone acetonide. Over 12 weeks, changes in POSAS 3.0 scores, degree of erythema and pigmentation, surface area, thickness, and pliability of the keloids will be measured at four different times: baseline, 4 weeks, 8 weeks, and 12 weeks. Statistical analysis will be conducted using SPSS software version 24, with a significance level of p < 0.05. DISCUSSION: Losartan potassium is believed to be beneficial for keloid management because it inhibits the angiotensin II receptor, which plays a role in inflammation, proliferation, and fibrosis. This study examines the efficacy of 5% losartan potassium loaded in ethosomal gel for human keloids. TRIAL REGISTRATION: Clinicaltrial.gov identifier NCT05893108 . Registered on 7 June 2023.

Characteristics and decreased Vitiligo Area Scoring Index of vitiligo patients with narrowband-UVB phototherapy in Yogyakarta, Indonesia.

Narrowband ultraviolet-B (NB-UVB) phototherapy is the mainstay of vitiligo therapy. The response can be evaluated using the vitiligo area scoring index (VASI) and repigmentation grade. However, few studies used VASI to evaluate phototherapy response and there are no definitive data on the reduction of VASI. This retrospective descriptive study aimed to determine the characteristics and decrease of VASI in patients with vitiligo after 36 and 48 sessions of NB-UVB phototherapy, conducted at Dr. Sardjito General Hospital, Yogyakarta, from December 2021-June 2022. The most common predilection was on the face (71.43%) and acral (61.90%). The most common responses after 36 and 48 phototherapy sessions were minimally improved (decrease in VASI<10%) and improved (reduction in VASI 10-25%). The mean decrease in VASI was 18% and 22% after 36 and 48 phototherapy sessions, respectively. 9.52% and 6.67% of patients experienced a reduction in VASI >50% after 36 and 48 phototherapy sessions, respectively. VASI assessment can be used to evaluate the response to phototherapy in vitiligo. However, VASI cannot show a reduction in vitiligo with slight repigmentation in slow-response patients.

Chronic kidney disease-associated pruritus in patients undergoing hemodialysis: Xerosis and topical therapy.

Chronic kidney disease-associated pruritus (CKD-aP) is a common and distressing symptom for patients with CKD and a difficult challenge for nephrologists and dermatologists. Recent results showed the multifactorial nature of the pathophysiology, and therapeutic trials were only successful in certain subsets of patients. The clinical manifestations are varied, with xerosis being the most common dermatological manifestation and correlated with the intensity of CKD-aP. A better understanding of the pathophysiology of xerosis in CKD-aP and appropriate topical treatment could correct xerosis to reduce the intensity of CKD-aP and improve the patient's quality of life.

Modified Non-Cultured Cell Spray Induced Epithelization in LAMB3 Mutation Epidermolysis Bullosa.

Background: Autologous non-cultured cell (ANCC) spray has been used to treat burns, chronic wounds, and vitiligo, but its use in junctional epidermolysis bullosa (JEB) has not been published previously. Chronic wounds in JEB are caused by mutations of laminin 332 (L322), whose function is to attach and act as a glue in the basal membrane. It is proposed that ANCC applications can provide keratinocytes and fibroblasts required to improve epithelization and spontaneously correct revertant keratinocytes in the wound area. Purpose: To develop a modified procedure of ANCC spray and improve epithelization using silver sulfadiazine covered with plastic wrap to treat chronic wounds of JEB. Patients and Methods: Shave excision of the donor site was performed on a 19-year-old girl with JEB. The ANCC spray was prepared and applied to the chronic wound, which was then covered with silver sulfadiazine occluded with plastic wrap. Results: Following the ANCC spray application, epithelization was successfully initiated. Unfortunately, the wounds recurred after four months of follow-up. Conclusion: The modified application method of ANCC spray provides a good alternative to treat chronic wounds in JEB.

Diffuse cutaneous mastocytosis masquerading as linear IgA bullous dermatosis of childhood.

Diffuse cutaneous mastocytosis is a rare form of cutaneous mastocytosis that can appear in heterogeneous clinical presentations, including eruption of papules, erythematous plaques, blisters, and erythroderma. We report a 1.5- year-old boy who presented with itchy wheals and blisters spreading on his body. The patient was initially managed as a linear IgA bullous dermatosis of childhood (LABD) because of the similarity of clinical symptoms and the presenting of linear IgA deposits at the basement membrane. Due to the development of urticarial plaque after the resolution of the blisters, the diagnosis of diffuse cutaneous mastocytosis was made based on clinical, histopathological (hematoxylin-eosin, Giemsa, and toluidine blue staining), and direct immunofluorescent examinations (IgA, IgG, IgM, C3). The symptoms were improved following antihistamines and oral corticosteroid treatment.

Inherited skin disorders presenting with poikiloderma.

Poikiloderma is a skin condition that combines atrophy, telangiectasia, and macular pigment changes (hypo- as well as hyperpigmentation). It is often mistaken for mottled pigmentation by general practitioners or nondermatology specialists. Poikiloderma can be a key presenting symptom of Rothmund-Thomson syndrome (RTS), dyskeratosis congenita (DC), hereditary sclerosing poikiloderma (HSP), hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP), xeroderma pigmentosum (XP), Bloom syndrome (BS), Kindler syndrome (KS), and Clericuzio-type poikiloderma with neutropenia (PN). In these conditions, poikiloderma starts early in life, usually before the second or third year. They may also be associated with photosensitivity and other significant multi-organ manifestation developed later in life. Poikiloderma could indicate the presence of a genetic disorder with potentially serious consequences. Poikiloderma almost always precedes more severe manifestations of these genodermatoses. Prompt diagnosis at the time of presentation could help to prevent complications and mitigate the course of the disease. This review discusses these to help the practicing clinician manage patients presenting with the symptom. To further facilitate early recognition, this paper also proposes a simple diagnostic algorithm.

Novel mutations of epidermolysis bullosa identified using whole-exome sequencing in Indonesian Javanese patients.

Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases known to have heterogenicity of phenotypes and genotypes. There are four main types of EB: simplex, junctional, dystrophic, and Kindler syndrome, which are further classified into 34 distinct subtypes. Twenty different gene mutations are responsible for the loss of function and integrity of the basal membrane zone. In limited-resource settings such as Indonesia, diagnoses of hereditary skin disease often rely on clinical features. This limitation was managed by using the Clinical Diagnostic Matrix EB for clinical diagnosis support and whole-exome sequencing for genetic analysis. This study is the first whole-exome sequencing analysis of Javanese Indonesian patients with EB. The genetic analysis from four patients with EB identified all novel mutations unreported in the dbSNP database. There are Kindler syndrome with FERMT1 frameshift mutation in exon 4, at c.388A (p.I130fs), which causes truncated protein; junctional EB generalized intermediate (JEB-GI) subtype with missense mutation at LAMB3 gene position c.A962C (p.H321P); and recessive dystrophic EB (RDEB) a missense mutation at COL7A1 gene position c.G5000T (p.G1667V). The whole-exome sequencing was further verified by Sanger sequencing. The new mutations' finding is possibly due to the limited genetic database in the Malayo-Polynesian ethnic group. Indonesia has hundreds of ethnic groups, and the Javanese is the largest ethnic group that populates Indonesia. Genetic data of these ethnic groups is important to be established in the international genetic database. This combination of clinical diagnostic and genetic analysis tools with whole-exome sequencing confirmed the challenging diagnosis of epidermolysis bullosa.

Follicular eruption as a cutaneous manifestation in COVID-19.

A 50-year-old man presented to our dermatology clinic with itchy skin rash. The rash began 5 days after systemic symptoms appeared such as mild fever and mild dyspnoea. The rashes were a characteristic of follicular eruption, which started on his stomach and spread all over his body. After a thorough evaluation, he was diagnosed with COVID-19 and was started on COVID-19 regimens. Skin lesions disappeared on the ninth day of treatment. Our findings contribute to the growing awareness of dermatological manifestations in patients with COVID-19.

Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome: a new case report from Indonesia and review of the literature.

BACKGROUND: DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures; MIM 220500) is a rare multisystem genetic disorder, mainly characterized by sensorineural deafness, shortened terminal phalanges with small nails of hands and feet, intellectual deficit, and seizures. The disease is caused by homozygous or compound heterozygous mutation in the TBC1 domain family member 24 (TBC1D24) gene (gene locus/MIM 613577) on chromosome 16p13. OBJECTIVES: We report the first case of DOORS syndrome from Indonesia. MATERIALS AND METHODS: A review of the literature was conducted and cases compared. RESULTS: A 27-day-old baby girl was brought to us with a history of recurrent seizures and absence of all finger- and toenails since birth. In addition, physical examination revealed left eye strabismus and a single transverse palmar crease on both hands. X-rays of the hands and feet showed absence of the distal phalanx of her right and left fingers II-V and the distal phalanx of her right and left toes I-V, respectively. Brainstem-evoked response audiometry test revealed profound bilateral sensorineural deafness. Pentalogy of Fallot was diagnosed by echocardiography, while an abnormal diffuse epileptiform pattern was found on electroencephalography. CONCLUSION: This is the first report of an association between pentalogy of Fallot and single transverse palmar crease in DOORS syndrome.

Oral and Topical Centella asiatica in Type 2 Diabetes Mellitus Patients with Dry Skin: A Three-Arm Prospective Randomized Double-Blind Controlled Trial.

INTRODUCTION: Uncontrolled diabetes mellitus (DM) is related to skin disorders, particularly dry skin. Pathogenesis of dry skin in type 2 diabetes mellitus (T2DM) rises from the chronic hyperglycemia causing an increase in advanced glycation end-products (AGEs), proinflammatory cytokines, and oxidative stress. Combination of oral and topical Centella asiatica (CA) is expected to treat dry skin in T2DM patients more effectively through decreasing N(6)-carboxymethyl-lysine (CML) and interleukin-1α (IL-1α) and increasing superoxide dismutase (SOD) activity. METHODS: A three-arm prospective, double-blind, randomized, controlled study was performed to evaluate the efficacy of the oral and topical CA extract in 159 T2DM patients with dry skin. The subjects were divided into the CA oral (CAo) 2 × 1.100 mg + CA topical (CAt) 1% ointment group, oral placebo (Plo) + CAt group, and Plo and topical placebo (Plt) group. Dry skin assessment was performed on day 1, 15, and 29, while evaluation of CML, IL-1α, and SOD activity was on day 1 and 29. RESULT: Effectivity of CAo + CAt combination was assessed based on HbA1c and random blood glucose (RBG). In well-controlled blood glucose, on day 29, the percentage of SRRC decrement was greater in the CAo + CAt group compared to the control group (p = 0.04). SCap value in the CAo + CAt group was greater than that in the control group (p = 0.01). In the partially controlled blood glucose, increment of SOD activity in the CAo + CAt group was greater than that in the control group (p = 0.01). There were medium-to-strong correlation between CML with SOD (r = 0.58, p < 0.05) and IL-1α with SOD (r = 0.70, p < 0.05) in well-controlled blood glucose. Systemic and topical adverse events were not significantly different between groups. CONCLUSION: CAo and CAt combination can be used to significantly improve dry skin condition through increasing SOD activity in T2DM patients with controlled blood glucose.