Drug Repositioning Using Temporal Trajectories of Accompanying Comorbidities in Diabetes Mellitus

Background@#Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates’ effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications. @*Methods@#Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records. @*Results@#We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44). @*Conclusion@#To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.

Topical ALA-Photodynamic Therapy for Acne Can Induce Apoptosis of Sebocytes and Down-regulate Their TLR-2 and TLR-4 Expression

BACKGROUND: Although photodynamic therapy (PDT) is widely performed for acne, little is known about its exact therapeutic mechanism. OBJECTIVE: We aimed to estimate the efficacy and safety of PDT on acne and to discover its mode of action. METHODS: We performed PDT on 12 patients with mild to moderate acne. The clinical efficacy was assessed by counting the acne lesions and measuring the sebum secretion before and after PDT. In addition, we took biopsy samples from the peri-lesional areas before and after 3-session of PDT. To examine the degree of apoptosis of the sebaceous follicles, TUNEL assay was performed. To investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after PDT, immunohistochemical stainings were also carried out. Finally, we performed TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in vitro after PDT. RESULTS: There was a significant reduction in the number of inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum excretion significantly decreased 2 weeks after the first PDT session except for one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous glands after PDT markedly increased, compared with those of before PDT. A decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after PDT was 50% and 30%, respectively. CONCLUSION: Our results demonstrate that apoptosis of the sebaceous glands is associated with improvement of acne by PDT. PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands and epidermis of acne patients.

Two Cases of Tick Bite Showing Localized Fat Herniation Response

The pathology related to a tick bite reaction is well described. Formation of a cavity below the mouthparts of the tick and mixed dense cellular dermal infiltration are general histopathologic findings of a tick bite. In addition, granuloma formation, vasculitic response, and panniculitis were reported. We present two cases of tick bite showing a new histopathologic finding, a localized fat herniation response.

A Case of Symmetric Dystrophic Calcinosis Cutis Following Subcutaneous Injections / 대한피부과학회지

Calcinosis cutis is the abnormal deposition of calcium phosphate into the skin. It is classified as dystrophic if the calcium is deposited in previously damaged tissue, and serum calcium and phosphorous levels are normal. We report a case of symmetric dystrophic calcinosis cutis on the both proximal arms of a 77-year-old woman who received a subcutaneous injection at each arm 30 years ago.

A Case of Granuloma Pyogenicum within a Port-wine Stain / 대한피부과학회지

Granuloma pyogenicum (GP) has been reported to be associated with hemangioma and hamartomas, including port-wine stains. GP may rarely occur in association with port-wine stains, either de novo or following trauma such as laser therapy. It has been suggested that the development of GP in a port-wine stain following trauma might be associated with microscopic arteriovenous anastomosis in the port-wine stain. We report a 48 year-old woman with GP arising within port-wine stain following trauma.

A Case of Total Dystrophic Onychomycosis Caused by Candida albicans in Diabetes Mellitus / 대한의진균학회지

Onychomycosis is the invasion of the healthy nail plate by species of dermatophytes, as well as a variety of non-dermatophytes (yeasts and moulds) which may cause nail infection, particularly after tissue damage by trauma or disease. Candida albicans and C. parapilosis are the most commonly isolated yeasts from abnormal toenails. The patient was a 20-year-old woman who presented with a thickened and crumbly nail plate of the right second finger for 4 months. Initially, a tiny yellowish macule appeared under the nail plate, which gradually involved the entire nail plate, resulting in complete deformity of the nail. She was diagnosed with diabetes mellitus 4 months ago and her blood sugar level was controlled with subcutaneous insulin injections. Direct microscopic examination of the scrapings prepared with potassium hydroxide revealed fungal elements. Repeated cultures on Sabouraud dextrose agar showed cream to white colored, semi-glossy, flat colonies, which were findings consistent with C. albicans. Complete extraction of the involved nail with meticulous curettage of the nail bed was made. She has been taking 150 mg of oral fluconazole weekly since August 2003 and showed substantial improvement.

A Case of Intradermal Nevus Clinically Mimicking Periungual Fibroma / 대한피부과학회지

We report a case of intradermal nevus in a 43-year-old female patient, who presented with a tender, solitary papule on the periungual area, which seemed to be a periungual fibroma. The skin biopsy revealed the upper dermis and lower dermis containing nests and cords of nevus cells without junctional activity. It was totally removed by excisional biopsy.

The Study of Post-adolescent Acne in Nurses / 대한피부과학회지

BACKGROUND: Acne is usually considered a disorder of adolescence, and a number of studies have examined the prevalence of this condition in the adolescent population. However, prevalence of acnes in patients over the age of 25 years has significantly increased. There are relatively few data on the prevalence of acne in the adult population, especially in Korea. Also, although many researches have been conducted into the etiology of this disease, much substantial myth still abounds with the treatment and cause of this condition. OBJECTIVE: This study was carried out to investigate the prevalence of acne in adult women, and to compare adolescent acne with post-adolescent acne in nurses. METHODS: We analyzed the answers from 504 nurses, who work in the St. Mary's Hospital, to questions about the acne. RESULTS: 1. Prevalence of post-adolescent acne was 36% in nurses of above the age of 25. Their mean age of onset of acne was 17.4 years. 2. The forehead and cheeks were the most common predilection sites in both groups. However, the jaw and perioral area were more common in the post-adolescent group than the adolescent group (p<0.05). 3. Positive family history of acne was more common in the post-adolescent group than the adolescent group (p<0.05). 4. Stress was the most important factor to aggravate acne in both groups. Menstrual cycle was related to aggravation of acne in the majority of nurses. However, both stress and menstrual cycle were more related to the post-adolescent group than the adolescent group (p<0.05). 5. Nurses are occupied medical care. Nevertheless, a considerable percentage of them showed wrong actions and incorrect recognition about the acne. CONCLUSION: Prevalence of post-adolescent acne in nurses was relatively high compared with previous data and most of post-adolescent acne was persistent acne.

A Case of Plantar Erythema Nodosum / 대한피부과학회지

Erythema nodosum is a reactive dermatosis that occurs in response to various stimuli, such as bacterial, fungal and viral infections, drugs and malignancies. Lesions of erythema nodosum usually appear symmetrically on the extensor aspects of the legs with occasional involvement of the thighs or forearms. Unilateral or plantar involvement uncommonly occurs. A 26-year-old man presented with bilateral, painful, multiple, confluent, erythematous, firm nodules confined to the both plantar skin for 7 days. Histopathologic examination revealed fibrosis of and a lymphohistiocytic infiltrate within the septae of fat lobules, consistent with erythema nodosum. We, herein, report an unusual case of plantar erythema nodosum, which was successfully treated with nonsteroidal antiinflammatory drugs for 2 weeks.

A Case of Acrometastasis in Renal Cell Carcinoma / 대한피부과학회지

Acrometastasis is rare and accounts for 0.1% of all metastasis. Renal cell carcinoma accounts for only 10% of this infrequent site. It is usually the late manifestation of a disseminated tumor, but may also be the primary manifestation of an occult cancer. Clinically, it may mimic benign tumors or nonneoplastic osteoarthritic conditions, thus resulting in misdiagnosis and improper treatment. We reported a case of acrometastasis in a renal cell carcinoma in a 76-year-old man who had been diagnosed with a progressed renal cell carcinoma with metastasis of the lung and brain.

Recurrent Seborrheic Keratosis on the Groin / 대한피부과학회지

Seborrheic keratoses (SK) are very common benign tumor arising in epidermis. Few malignant transformation of SK were reported. Inflammation, ulceration or atypical nature is the evidence of malignant transformation. Some melanoma can mimic SK. So, all SK need confirm histopathologic diagnosis. We reported a case of recurrent seborrheic keratosis with satellite lesions on the left groin in a linear pattern in a 46-year-old man.

A Case of Seborrheic Keratosis Showing Zosteriform Distribution / 대한피부과학회지

Seborrheic keratosis is a common skin disease in the elderly, and when multiple lesions are present, scattered distribution is the rule. Here we present a case of seborrheic keratosis showing zosteriform distribution. The patient was a 41-year-old female whom since childhood presented multiple brownish or black colored papules on her right back. The papules were linearly grouped, thereby showing zosteriform distribution. The histopathologic findings revealed a typical acanthotic type of seborrheic keratosis. As we know, this type of distribution in seborrheic keratosis has not been reported so far.

A Case of Actinic Keratosis Treated with Topical Imiquimod / 대한피부과학회지

Actinic keratoses (AK) are premalignant lesions, which can develop into invasive squamous cell carcinoma(SSC). Therapies for AK include cryotherapy, curettage, topical 5-fluorouracil, laser therapy and so forth. All therapies currently prescribed can be painful and may result in scarring and changes in skin pigmentation. A potential new treatment modality for AK is the imiquimod (Aldara(R)), which can be applied by patients themselves. We reported a case of AK which was very extensive on the scalp of the old man, who was treated with topical imiquimod.