Byoung Joon So

Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats.

Intense focused ultrasound for facial tightening: Histologic changes in 11 Patients

Abstract Introduction: Intense focused ultrasound (IFUS) is a novel modality for treating skin laxity that produces thermal effects at various depths while sparing the overlying tissue. This study assessed histologic changes and the safety and efficacy of intense focused ultrasound (DoubloTM, HIRONIC Co., Sungnam, Korea) for tightening of facial skin in Asian patients. Methods: Eleven patients with facial laxity were treated with IFUS and evaluated before and after treatment. Mean age was 46 years (range, 35–64 years). Two available hand-pieces with different focal depths (3 mm and 4.5 mm) were used with three to five passes 1–2 mm apart. Outcome assessment included photographic evaluation by two blinded investigators, skin biopsies before and two months after treatment, and patient satisfaction. Results: Subjective and objective analyses showed 63.6% and 72.7% improvement at the two-month evaluation, respectively. Histologic evaluation by hematoxylin and eosin (H&E) and Massons trichrome staining showed increased collagen fibers in the lower dermis and between fat layers. Discussion and conclusions: Intense focused ultrasound can be used as a non-invasive skin tightening technique in Asian patients. It induced collagen generation in the dermis and fat layers and was effective and safe in our study population.

Successful Treatment of Livedoid Vasculitis with Primary Antiphospholipid Syndrome by Using Aspirin and Low Dose Warfarin Combination Therapy.

Dear Editor: Livedoid vasculitis is a rare disorder clinically characterized by purpuric macules and papules on the lower legs and feet1. These lesions are caused by infarction of small vessels that affects young and middle-aged women. The bizarrely shaped ulcers may be painful, heal slowly, result in scarring, or cause atrophie blanche2. Livedoid vasculitis usually occurs in isolation; however, several reports have shown an association with systemic lupus erythematosus, other autoimmune diseases, and malignant disease3. However, an association with antiphospholipid antibodies has been rarely described. Antiphospholipid syndrome is an acquired hypercoagulable state, shows recurrent thrombosis, and can spontaneously resolve. It is correlated with systemic lupus erythematosus in about half of the patients. There are only a few reports about patients with livedoid vasculitis accompanying primary antiphospholipid syndrome without systemic lupus erythematosus. Primary antiphospholipid syndrome could be diagnosed by using the criteria of Miyakis et al.4 (small vessel thrombosis, spontaneous abortion/anticardiolipin antibody subclass immunoglobulin (Ig) G or IgM, anti-β2 glycoprotein IgG or IgM, and lupus anticoagulant). A 33-year-old female patient with painful tender erythematous ulcers on both lower legs visited our hospital in December 2012. The ulcers had been covered with exudate and crust for 4 months. She had been treated with a nonsteroidal anti-inflammatory drug for several months before visiting our institution. Irregular ulceration and purpura were observed on admission (Fig. 1A). Histological examination showed evidence of dilated capillaries in the upper dermis and thickened vessel walls containing fibrinoid materials (Fig. 2). She was initially treated with systemic methylprednisolone, but she failed to respond. Screening for vasculitis gave normal results, including lupus relevant antibodies (lupus anticoagulant, antinuclear antibody, and anti-dsDNA antibody), except for the increase in anti-cardiolipin antibody subclass IgG at 17.2 U/ml (reference, <9 U/ml) and a markedly increased anti-cardiolipin antibody subclass IgA at 20.8 U/ml (reference, <10 U/ml). Additionally, she had increased anti-phospholipid antibody subclass IgG at 18.4 U/ml. Therefore, the diagnosis was concluded to be livedoid vasculitis and primary antiphospholipid syndrome, and she was started on combination therapy with 100 mg aspirin and low-dose warfarin (2 mg) daily with a good clinical response (Fig. 1B). She remains in remission presently. Fig. 1 (A) Lesions showing purpura and irregular ulcerations at first visit. (B) Lesions showing almost complete clinical remission at 2 months after treatment. Fig. 2 (A) Dilated capillaries in the upper dermis (H&E, ×40). (B) Vessel walls are thickened and contain fibrinoid material (H&E, ×100). The treatment for livedoid vasculitis with antiphospholipid syndrome is not clearly defined. Corticosteroids have been used successfully5; however, they do not provide long-term benefits, and our patient showed no response. Antithrombotic agents, including tissue plasminogen activator, prostacyclin, antiplatelet therapy, and low-dose warfarin, can be used successfully1,2,3. The combination of low-dose warfarin and antiplatelet therapy was used in our patient to prevent further thrombosis. The patient demonstrated histologically thickened vessel walls containing fibrinoid material and clinically irregular ulcerations and purpura. Therefore, her condition was diagnosed as livedoid vasculitis with primary antiphospholipid syndrome and she was treated with low-dose warfarin, an antiplatelet agent. Livedoid vasculitis presents the clinical symptoms of other diseases that cause occlusive vasculopathy; thus, clinicians should find the underlying conditions and provide treatment if antiphospholipid antibodies are present. Aspirin and low-dose warfarin combination therapy is a valuable therapeutic option for livedoid vasculitis with primary antiphospholipid syndrome.

Treatment of Diffuse Planar Xanthoma of the Face after One Session of 1,444-nm Neodymium-Doped Yttrium Aluminium Garnet Laser.

Dear Editor: A 41-year-old man presented with a 10-year history of progressive diffuse plane xanthoma of the face, neck, upper extremities, and flank (Fig. 1). His triglyceride, lipoprotein, and cholesterol levels were normal. Other conditions (e.g., monoclonal gammopathy, lymphoproliferative disease, or normolipemic xanthomatous skin disease) were excluded on the basis of findings from lipid electrophoresis and immunoelectrophoresis, blood cell counts, radiography of the skull, and electron microscopy, which were consistent with diffuse idiopathic plane xanthoma. He received multiple CO2 laser treatments at other hospitals, but with no curative effect. We proposed to remove the plane xanthoma with a 1,444-nm neodymium-doped yttrium aluminium garnet (Nd:YAG) laser (AccuSculpt; Lutronic Corporation, Goyang, Korea). Two 1×1 cm2 test areas, one on each earlobe, were treated with 1,444-nm Nd:YAG laser by external beam irradiation with 80 J in total by using the following treatment parameters: pulse energy, 100 mJ; pulse rate, 20 Hz (power, 2.0 W). In both areas, the lesions were ablated into the superficial dermis until papillary bleeding occurred. After 1 month, both test areas showed resolution of the lesions without recurrence. Then, a 1,444-nm Nd:YAG laser was used for the full-face plane xanthoma lesions. The full-face plane xanthoma lesions were destroyed by irradiating with 918 J in total by using the external beam with the same treatment parameters as the test shots. Postoperatively, hydrocolloid dressings (DuoDERM Extrathin; Convatec International, Skillman, NJ, USA) together with antiseptic ointment were applied until reepithelization. After 1 month, the lesions showed erythema and some atrophic scars. There were no residual xanthoma lesions after 6 months; however, scar formation on the right lower cheek and textural changes in at least 50% of the treated area were observed (Fig. 2). Fig. 1 Plane xanthoma. Yellowish maculopapular lesions had spread over the entire face. Fig. 2 Six months after the full lesional treatment, focal and mild textural changes and scarring are observed. Most therapeutic options in the treatment of plane xanthoma are based on mechanical removal through excision, chemabrasion, dermabrasion, or ablative laser therapy1. Several studies suggest that the 1,444-nm laser achieves superior lipolysis compared with other laser wavelengths2,3,4. Theoretically, more effective laser lipolysis is anticipated with the 1,400-nm wavelength because it has a >10-fold higher affinity to fat than the 1,064-nm wavelength3. Youn and Holcomb2 indicated that the 1,444-nm wavelength provided both the highest efficiency for fatty tissue ablation and the greatest thermal confinement compared with the 1,064- and 1,320-nm wavelengths. Tark et al.3 reported a marked reduction in fat volume identified by using in vivo minipig and in vitro human fat experiments, with the 1,444-nm wavelength compared with the 1,064-nm wavelength. However, the mechanism of action of this laser in the treatment of xanthomas may depend not only on thermal lipolysis but also on nonspecific thermal effects. Superficial scar formation due to thermal damage to the surrounding tissue may act as a shield covering the leftover lesions underneath. To the best of our knowledge, this is the first study to describe the clinical application of a 1,444-nm laser for the treatment of xanthoma. In conclusion, 1,444-nm Nd:YAG laser therapy is an alternative treatment for facial diffuse plane xanthoma that shows fast reepithelialization. However, the risk of skin textural change and scar formation remains a challenge.

A Case of Gonadotropin-Releasing Hormone Agonist-Induced Sterile Abscess Showing a Good Response to Systemic Steroid Therapy.

Dear Editor: Prostate cancer is a common malignancy in men, and its incidence is increasing rapidly. Because prostate cancer shows androgen dependency in the early stages1, androgen-deprivation therapy with gonadotropin-releasing hormone (GnRH) agonists is the most effective systemic treatment2. Leuproreline (Lucrin; Abbot, Amstelveen, The Netherlands) is a GnRH agonist that blocks pituitary GnRH receptors, leading to the downregulation of luteinizing hormone and follicle-stimulating hormone3. This chemical castration provides long-term maximal androgen deprivation1. A 79-male-old man, who had painful tender erythematous subcutaneous nodules on the abdomen, visited our dermatologic department in June 2012. He received androgen-deprivation therapy consisting of pretreatment with leuprorelin 11.25 mg at 3-month intervals to treat underlying prostate cancer. A lesion arose from a previous leuprorelin injection site 2 weeks after the last injection (Fig. 1A). He was initially treated with antibiotics and non-steroidal anti-inflammatory drugs, but no improvement was observed. Subsequent histological examination showed neutrophilic and eosinophilic infiltration in the reticular dermis (Fig. 2). Laboratory examination results, including bacterial culture and tuberculosis polymerase chain reaction, were negative. Therefore, he was diagnosed with a sterile abscess caused by GnRH agonist injection and treated with systemic methylprednisolone 16 mg/day. The lesion had almost cleared after 4 weeks and remains in remission as of writing (Fig. 1B). Fig. 1 Painful tender erythematous subcutaneous swelling on abdomen. (A) Before treatment. (B) After 4 weeks of systemic steroid therapy. Fig. 2 Histologic slide stained with hematoxylin and eosin reveals neutrophilic and eosinophilic infiltrates in the reticular dermis. Leuprorelin, a GnRH agonist, is the most effective therapeutic modality for prostate cancer. Although GnRH agonist therapy appears to have significant benefits for patients, it also has serious side effects including anemia, cognitive changes, obesity, lipid alterations, insulin resistance, coronary artery disease, and osteoporosis2,3. The efficacy and side effects of GnRH agonists have recently been reported. In particular, sterile abscess formation has been reported in 3% of patients who received a GnRH agonist4. In Korea, only two patients, who were injected with a GnRH agonist for the treatment of central precocious puberty, have been reported to have developed a sterile abscess at the injection site5. Thus, our case is the first case of a sterile abscess in a Korean patient with prostate cancer treated with leuprorelin. There are many theories about the cause of sterile abscess5. One possible cause is an additive polymer of leuprorelin similar to that used in resorbable sutures. However, there is a report about granulomatous reactions induced by leuprorelin alone3. Thus, this could be thought of as a positive allergic reaction to leuprorelin. Furthermore, these reactions occurred in patients who received daily subcutaneous leuprorelin injections without additive polymer5. Thus, these cases suggest leuprorelin itself could be the cause of sterile abscess and granulomatous reaction. Previous reports describe spontaneous healing of sterile abscesses over several months without treatment4,5. Our patient was treated with a systemic steroid and remained in remission for 1 month. Thus, systemic steroid therapy may be a potential therapeutic modality for GnRH agonist-induced sterile abscess. Dermatologic clinicians should be aware of the potential adverse effects of leuprorelin injection, including sterile abscess and granulomatous reactions.

Effects of Korean red ginseng as an environmental skin barrier function

Dry skin dermatitis is a common skin disease, associated with aging and environmental changes. Damaged skin from xerosis can be evaluated with several objective methods such as D-squame, transepidermal water loss (TEWL), corneometer, and a pH meter. Forty-two patients with xerosis participated in this study. We assessed the effects of Korean red ginseng after 6 weeks of taking the medicine. Patients who treated with Korean red ginseng were clinically improved but the results were measured by D-squame, TEWL, corneometer, and a pH meter did not show statistical significant. These data indicate that Korean red ginseng may be a useful health supplement. However, further study that include more large patients’ group would be required.

Epidermotropic metastatic melanoma clinically resembling agminated spitz nevi.

Herein, we report a 36-year-old Asian male patient who presented with grouped multiple erythematous waxy papules and nodules on his right medial thigh. He had undergone amputation of the right second toe because of a stage IIa malignant melanoma, 3 years previously. At the time of surgery for the primary tumor, right inguinal lymph node dissection revealed no nodal involvement. Three years after the diagnosis of the primary tumor, crops of multiple erythematous papules and nodules developed. Initial histopathologic evaluation of the papules showed nests of small epithelioid cells similar to compound nevi. However, cytologic features, including high mitotic figures, lack of maturation, and some hyperchromatic nuclei suggested metastatic melanoma. In addition to the pathologic findings, the tumors were on the right thigh, which was the same side as the primary malignant melanoma. The patient underwent wide excision of the tumor and split-thickness skin grafting.