Search

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease characterized by relapsing and remitting flares of sterile neutrophilic pustules and systemic inflammation. The definition of GPP is inconsistent globally, with large discrepancies in clinical management. To provide clinical guidance on managing GPP, we conducted a systematic literature search for articles published within the last decade on PubMed and the Cochrane Library in October 2022 and held four consensus meetings with 12 Taiwanese dermatologists between October 2022 and July 2023. Upon review of 153 articles, we agreed to adopt the European Rare and Severe Psoriasis Expert Network GPP definition with additional clarifications on pustular flares in psoriatic plaques, circinate or annular lesions, and localized pustules. We also drafted a diagnostic algorithm to facilitate GPP diagnosis. Twenty-seven statements on GPP treatment reached consensus. We recommend using an oral retinoid or spesolimab injection for the first-line treatment in both acute (treating flares) and maintenance (preventing flares) settings in adults with GPP. For infants and juveniles with GPP, retinoids are recommended as a first-line treatment. Evidence for other conventional and investigational therapies was reviewed, and a treatment algorithm was proposed. We hope this consensus provides practical guidance for clinicians in Taiwan and helps improve outcomes for GPP patients.

Objectives: Alopecia is a soft but meaningful complaint affecting women's physical and psychological health. Female alopecia (FA) has diverse etiologies. Nonetheless, FA is stereotyped as female pattern hair loss, also known as female androgenetic alopecia, and has not been thoroughly investigated. This study aimed to identify the etiologies of FA at a tertiary medical center in Eastern Taiwan. Materials and Methods: This retrospective study enrolled female patients with hair loss who visited the dermatology department of (blinded information). A complete history taking was obtained, including the onset and duration of alopecia, menstruation, gynecologic diseases, psychological stress, underlying diseases, vaccination, and dietary habits, etc., Blood tests were performed, including hemoglobin (Hb), ferritin, Zn, autoimmune and thyroid profiles, etc., Iron deficiency (ID) was defined as serum ferritin level

Objectives: Orthopedic implants have improved the quality of life in aging society but also induces several kinds of tissue reactions, referred to as orthopedic implant hypersensitivity (OIH). The aim of our study is to report the clinical characteristics of OIH and the effects of photobiomodulation therapy (PBMT) on these groups of patients. Materials and Methods: We collected cases that complained of skin rashes with pruritus after orthopedic implants from January 2017 to June 2022 at the Dermatology clinic in Hualien Tzu Chi Hospital. We recorded the sites and material of orthopedic implants, skin lesions onset time, symptoms, location after implantation, and the disease duration. Laboratory tests were measured, including complete blood count, differential count, serum immunoglobulin E (IgE) level, as well as inflammatory and autoimmune markers. PBMT, including UVB311 nm or low-level laser therapy 808 nm, was performed. Dose, duration, and response were documented. Results: Fourteen patients were diagnosed with OIH; twelve presented with localized eczema at the implant sites, and two with generalized eczema. Eleven patients (78.6%) had either elevated eosinophils percentage (>6%) or IgE level (>200 U/mL) or both. Seven patients (50%) had favorable outcome after PBMT and successfully withdrew from systemic steroid. Conclusion: In our case series, localized eczema at implant sites was a common cutaneous presentation in OIH. Hence, a surgical scar at the eczema site or long-term waxing and waning generalized eczema should prompt physicians on the possibility of OIH. Blood eosinophils percentage and serum IgE level can be reference biomarkers for OIH. PBMT provides a noninvasive and effective treatment strategy for immune regulation and tissue regeneration.

Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, is a novel targeted therapy for advanced-stage breast cancer. Although ribociclib-induced cutaneous side effects have been previously noted, they have not been well documented. Herein, we present a case of ribociclib-induced phototoxicity, which manifested as dyschromia over sun-exposed forearms and neck initially and as bullae formation subsequently. A 71-year-old woman with metastatic breast cancer developed dyschromia after daily treatment with ribociclib (600 mg) for 7 months. Skin biopsy of the pigmented lesion revealed interface dermatitis with melanin incontinence and dyskeratotic cells and ballooning keratinocytes with loss of melanocytes in the basal layer. Further, clefting at the basal layer of epidermis was noted in a more hyperpigmented field. Fontana–Masson staining revealed melanophages in the dermis. Human Melanoma Black-45 staining revealed decreased melanocyte numbers in the epidermis above the cleft. Immunohistochemical analyses revealed activated CD1a+ epidermal Langerhans cells and infiltrating CD4+ and CD8+ T cells in the epidermis and dermis, thereby indicating type IV hypersensitivity that was associated with damage to keratinocytes and melanocytes. To prevent progression of bullous dermatitis, we advised the patient to discontinue ribociclib and prescribed oral and topical prednisolone. Due to the risk of phototoxicity, we educated the patient on sun-protection strategies. The patient’s skin lesions subsided during the 2 months of treatment. Phototoxicity with dyschromia is a rare but significant ribociclib-induced cutaneous side effect. Early diagnosis, rapid ribociclib withdrawal, protection from sunlight, and prompt treatment are critical for preventing subsequent severe bullous dermatosis.

Melanocytic nevi, dysplastic nevi, and melanoma are all derived from the pigment-producing cells, namely melanocytes. Concerning the clinical spectrum, cutaneous melanoma is the most aggressive skin cancer with a low survival rate, while nevi are the most common benign lesions in the general population, and dysplastic nevi place in between nevi and melanoma. Ultraviolet (UV) radiation is a well-recognized extrinsic risk factor for all three. BRAFV600E is a well-recognized driver mutation that activates the RAS-BRAF-mitogen-activated protein kinase (MAPK) signaling pathway among 40%–60% of melanoma cases. Interestingly, BRAFV600E mutation is detected even more in acquired nevi, approximately 80%. However, in nevi, several tumor suppressors such as p53 and phosphatase and tensin homolog (PTEN) are intact, and senescence factors, including p15INK4b, p16INK4a, p19, and senescence-associated acidic β-galactosidase, are expressed, leading to cell senescence and cell cycle arrest. Although loss of p53 function is rarely found in melanoma, decreased or loss of PTEN with an activated PI3k/Akt signaling pathway is common in nevi, which may abolish senescence status and allow further progression into dysplastic nevi or melanoma. At present, mouse models closely resembling human nevi are used for investigating these phenomena. Melanocortin 1 receptor deficiency, an intrinsic risk factor for melanomagenesis, is related to the production of procarcinogenic pheomelanin and the inhibition of PTEN function. Immune response escape via programmed cell death-1/programmed cell death ligand-1 interaction plays further roles in monitoring the spectrum. Here, we review the current literature on the molecular and immune mechanisms involving the transition from benign nevi to malignant melanoma.

Disseminated herpes zoster (DHZ), resulting from the reactivation of the varicella-zoster virus (VZV), typically occurs in immunocompromised persons. To date, only four cases of DHZ following mRNA, viral vector, or inactivated COVID-19 vaccinations have been reported in immunocompetent patients. Herein, we present the first case of DHZ following the protein subunit COVID-19 vaccination (case 1, 64 years old) and a case of DHZ following mRNA COVID-19 vaccination (case 2, 67 years old) in elderly, immunocompetent male patients. Both cases were generally healthy, without a remarkable underlying disease and without a history of immunosuppressant use. Case 1 developed DHZ (left C3–5 predominant) 1 month after receiving the third dose of the SARS-CoV-2 spike protein vaccine (MVC-COV1901). Case 2 developed DHZ (right V1–3 predominant) 7 days after receiving the second dose of the mRNA-1273 SARS-CoV-2 vaccine. Through skin examination, Tzanck smears, and dermoscopy, the diagnosis of COVID-19 vaccination-related DHZ was established in both cases. Oral famciclovir (250 mg, three times/day for 7 days) was administered, and both cases achieved total remission of skin lesions without visceral involvement or severe post-herpetic neuralgia. Our cases demonstrate that DHZ, as a rare cutaneous adverse event in immunocompetent patients, can be secondary not only to mRNA COVID-19 vaccination but also to the protein subunit COVID-19 vaccination. It is speculated that the spike protein of SARS-CoV-2 could be the common trigger for the reactivation of VZV among different types of vaccinations.

Melanoma is fatal for skin cancer. One of the essential predictive points in melanoma progression is the development of dysplastic nevi. This study observes subcutaneous blood vessels, lymphatic vessels, and skin thickness in a mouse model of dysplastic nevi in vivo through noninvasive, high-resolution, and multi-contrast optical coherence tomography (MCOCT). The subcutaneous microenvironment of the mice showed increased density of lymphatic vessels, dilated walls, and increased thickness of ears during the change of dysplastic nevi; and fragmentation of blood vessels at the later stage of the experimental period. Compared with conventional OCT only provides structure anatomy, MCOCT provides more extensive information for disease analysis and has the potential to detect progressive changes in dysplastic nevi.

Melanoma is a high-risk skin cancer because it tends to metastasize early and ultimately leads to death. In this study, we introduced a noninvasive multifunctional optical coherence tomography (MFOCT) for the early detection of premetastatic pathogenesis in cutaneous melanoma by label-free imaging of microstructures (i.e., providing the thickness and the scattering information) and microcirculation (i.e., providing depth-resolved angiography and lymphangiography). Using MFOCT-based approaches, we presented an in vivo longitudinal observation of the tumor microenvironment in Braf V600E/V600E;Pten−/− mice with inducible melanoma monitored for 42 days. Quantitative analysis of MFOCT images identified an increased number of lymphatic and vascular vessels during tumor progression and faster lymphangiogenesis (beginning on day 21) than angiogenesis (beginning on day 28) in the melanoma microenvironment. We further observed lymphatic vessel enlargement from the first week of melanoma development, implying tumor cells interacting with the vessels and increased likelihood of metastasis. MFOCT identified cutaneous melanoma‒associated angiogenesis and lymphangiogenesis before the possible visual perception of the tumor (≥42 days) and before metastasis could be diagnosed using micropositron emission tomography (35 days). Thus, the proposed quantitative analysis using MFOCT has the potential for early detection of cutaneous melanoma progression or prediction of metastatic melanoma in a mouse model. However, retrospective and extensive experiments still need to be performed in the future to confirm the value of MFOCT in clinical application.

Acquired reactive perforating collagenosis (ARPC) is a rare condition caused by transepidermal elimination of collagen, elastin fibers and keratin. To date, the pathogenesis of ARPC remains unknown. Different hypotheses were proposed, including superficial microtrauma due to pruritus and subsequent scratching, diabetes-induced microangiopathy, epidermal and dermal abnormalities in metabolic disorders, dermal microdeposits in patients with chronic renal failure and vasculopathy underlying chronic venous insufficiency and hypertension. In the past two decades, oral allopurinol had been found to be effective in treating ARPC. We report a case of a 36-year-old pregnant woman with itchy skin lesions on the trunk and four limbs since 36 weeks of her gestation. Initially, she was prescribed with oral antihistamine and topical steroid but did not respond well. Skin biopsy was performed and was compatible with ARPC. Normal renal and liver function tests were noted, and the HLA-B5801 test was negative. We treated the patient with allopurinol. Significant improvement was noticed at 1-month follow-up. To the best of our knowledge, this is the first case successfully treating ARPC induced by pregnancy with allopurinol. On careful follow-up of laboratory data and HLA-B5801 test screening, allopurinol may be another effective treatment option for ARPC patients after pregnancy.

A 56-year-old woman presented with multiple blisters on the rim of painful erythematous annular lesions over the trunk and four extremities, accompanied with fever and arthralgia on both ankles and feet. Laboratory studies showed neutrophilia and elevated C-reactive protein level. Skin biopsy revealed exuberant edema of the papillary dermis, extensive neutrophil infiltration, and hemophagocytosis within the dermis. Her symptoms and skin lesions resolved 3 days after initiation of systemic corticosteroids. To the best of our knowledge, this is the first case report of cutaneous hemophagocytosis without additional symptoms of hemophagocytic syndrome in patients with Sweet's syndrome.

Granulocyte colony-stimulating factor (G-CSF) was reported to have a neuroprotective effect in a rat model of anterior ischemic optic neuropathy (rAION model). However, the therapeutic window and anti-inflammatory effects of G-CSF in a rAION model have yet to be elucidated. Thus, this study aimed to determine the therapeutic window of G-CSF and investigate the mechanisms of G-CSF via regulation of optic nerve (ON) inflammation in a rAION model. Rats were treated with G-CSF on day 0, 1, 2 or 7 post-rAION induction for 5 consecutive days, and a control group were treated with phosphate-buffered saline (PBS). Visual function was assessed by flash visual evoked potentials at 4 weeks post-rAION induction. The survival rate and apoptosis of retinal ganglion cells were determined by FluoroGold labeling and TUNEL assay, respectively. ON inflammation was evaluated by staining of ED1 and Iba1, and ON vascular permeability was determined by Evans Blue extravasation. The type of macrophage polarization was evaluated using quantitative real-time PCR (qRT-PCR). The protein levels of TNF-α and IL-1β were analyzed by western blotting. A therapeutic window during which G-CSF could rescue visual function and retinal ganglion cell survival was demonstrated at day 0 and day 1 post-infarct. Macrophage infiltration was reduced by 3.1- and 1.6-fold by G-CSF treatment starting on day 0 and 1 post-rAION induction, respectively, compared with the PBS-treated group (P

Mycosis fungoides (MF) is a form of cutaneous T cell lymphoma defined by epidermotropism of a clonal T helper memory/effector subset. Erythrodermic MF usually presents a chronic course of MF with generalized erythema or poikiloderma but no systemic involvement, as in Sezary syndrome. Here we report a case of a 73-year-old Taiwanese male with a rapid progression of erythrodermic MF within 1.5 years. It was diagnosed after his fifth skin biopsy, which demonstrated a positive clonal band in the T cell receptor Dβ-Jβ and Vγf1-Jγ gene. The sequential skin manifestations were eczema and contact dermatitis–like well-defined skin lesions over the back with the pathological characters of interface dermatitis and psoriasiform dermatitis, respectively. He was treated with oral bexarotene (prescribed in the United States) but found the side effects intolerable. We administered low-dose methotrexate (MTX, 7.5–15 mg/wk) and 311 nm UV-B for the erythrodermic MF. After 3 years of treatment, the skin lesions completely subsided, and a skin biopsy showed no more clonal T cells. Flow cytometry analysis revealed the decline of the HLA-DR+ T helper cell ratio in peripheral blood during MTX administration and parallel with the cutaneous improvement. Inhibition of histone deacetylase activity has been identified to be a novel function of MTX. We propose that MTX can be an effective and safe treatment for erythrodermic MF. The mechanisms of MTX in cutaneous T cell lymphoma, especially the role of immunomodulation and histone deacetylase inhibition, are reviewed.

Psoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7–9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7–9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7–9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7–9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs.

Background: Previous studies have shown that topical corticosteroid (TCS) use induces structural abnormalities of the stratum corneum (SC), resulting in permeability barrier disruption. It is well-known that epidermal barrier perturbation induces a cytokine cascade, leading to cutaneous inflammation. Accordingly, we hypothesize that barrier disruption caused by long-term TCS therapy may trigger a cutaneous cytokine cascade, which plays an important role in withdrawal dermatitis (WD) following discontinuation of TCS. The objective of this study was to elucidate the possible mechanism of WD. Methods: Hairless mice were treated once daily with 0.064% betamethasone dipropionate ointment for 6 weeks. After discontinuation of TCS, we examined the transepidermal water loss (TEWL), SC lipids and expression of the cytokines interleukin 1-alpha (IL1-α) and tumor necrosis factor-alpha (TNF-α) and their downstream signaling pathway in the following 2 weeks. Results: We observed upregulation of IL1-α, TNF-α, inhibitor of nuclear factor kappa-B kinase subunits alpha and beta (IKK1, IKK2) and nuclear factor kappa-B (NF-κB) in the epidermis, accompanied by a significantly higher TEWL after TCS cessation. These cytokines gradually disappeared with concomitant normalization of TEWL after 1 week. Only negligible amounts of the aforementioned cytokines were observed in the dermis. Furthermore, concurrent application of petrolatum during TCS treatment decreased barrier impairment and production of cytokines. Conclusion: An epidermis-derived cytokine cascade was observed following TCS-induced barrier disruption, which is similar to that from permeability barrier insults by acetone or tape stripping. The study suggests that concurrent application of skin care products during TCS treatment improves barrier homeostasis, and should become a standard practice to alleviate TCS-induced WD.

Imatinib, a tyrosine kinase inhibitor, is the current preferred agent for the treatment of unresectable or metastatic dermatofibrosarcoma protuberans (DFSP). We present the first case report with exacerbated psoriasis during imatinib treatment for recurrent DFSP. The condition of a 63-year-old man with a history of psoriasis vulgaris for 17 years was controlled well by topical calcipotriol. He suffered from a recurrent DFSP, and the molecular pathology analysis showed OL1A1–PDGFB fusion transcript. Imatinib (400 mg daily) was commenced after surgical excision, and 4 weeks later he developed generalized psoriasis that was poorly controlled by regular treatment. After discontinuation of imatinib, combined with systemic antihistamine and topical corticosteroid, the lesions improved in 8 weeks. We further reviewed the literature to characterize the imatinib-induced psoriasis.

To investigate the effects of cerebrolysin (Cbl) on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of ON crush. Rats received intravitreal injection of Cbl (n = 20), intra-ON injection of Cbl (n = 20), intraperitoneal injection (IPI) of Cbl (n = 20), or phosphate buffered saline (PBS; n = 20) every day for 2 weeks after ON crush injury. At 3 weeks post-trauma, RGC density was counted by retrograde labeling with FluoroGold and visual function was assessed by flash visual-evoked potentials. Activities of microglia after insults were quantified by immunohistochemical analysis of the presence of ED1 in the optic nerve. At 3 weeks postcrush, the densities of RGCs in the Cbl-IVI group (1125 ± 166/mm2) and in the Cbl-IPI treatment group (1328 ± 119/mm2) were significantly higher than those in the PBS group (641 ± 214/mm2). The flash visual-evoked potential measurements showed that latency of the P1 wave was significantly shorter in the Cbl-IVI- and Cbl-IPI-treated groups (105 ± 4 ms and 118 ± 26 ms, respectively) than in the PBS-treated group (170 ± 20 ms). However, only Cbl IPI treatment resulted in a significant decrease in the number of ED1-positive cells at the lesion sites of the ON (5 ± 2 cells/vs. 30 ± 4 cells/high-power field in control eyes). Treatment with intra-ON injection of Cbl was harmful to the optic nerve in the crush model. Systemic administration of Cbl had neuroprotective effects on RGC survival and visual function in the optic nerve crush model.

Giant condyloma acuminatum (Buschke–Löwenstein tumor) is a rare sexually transmitted disease caused by human papilloma virus infection in the anogenital area. It is characterized by rapid growth, large size, local destruction, lack of spontaneous resolution, poor response to conservative therapy (e.g., cryotherapy), and a high recurrence rate. Treatment of such tumors remains challenging. We report the case of a 56-year-old Taiwanese man with a 9-month history of the Buschke–Löwenstein tumor with rectal invasion, treated by topical photodynamic therapy. We applied 16% methyl aminolevulinate for 3 hours and irradiated the tumor with 630-nm light at a dose of 37 J⁄cm2 every 4–6 weeks. After three therapy sessions, the tumor disappeared without any scar or anal function impairment. Remote lesions that had been identified in the rectum also disappeared. Pain was the main side effect during treatment, but it was controlled by oral gabapentin. No recurrence was noted at 12-month follow-up or to date.

Orientia (O.) tsutsugamushi-induced scrub typhus is endemic across many regions of Asia and the Western Pacific, where an estimated 1 million cases occur each year; the majority of patients infected with O. tsutsugamushi end up with a cytokine storm from a severe inflammatory response. Previous reports have indicated that blocking tumor necrosis factor (TNF)-α reduced cell injury from a cytokine storm. Since TNF-α production is known to be associated with intracellular Ca2+ elevation, we examined the effect of store-operated Ca2+ entry (SOCE) inhibitors on TNF-α production in O. tsutsugamushi-infected macrophages. We found that 2-aminoethoxydiphenyl borate (2-APB), but not SKF96365, facilitates the suppression of Ca2+ mobilization via the interruption of Orai1 expression in O. tsutsugamushi-infected macrophages. Due to the decrease of Ca2+ elevation, the expression of TNF-α and its release from macrophages was repressed by 2-APB. In addition, a novel role of 2-APB was found in macrophages that causes the upregulation of heat shock protein 70 (HSP70) expression associated with ERK activation; upregulated TNF-α production in the case of knockdown HSP70 was inhibited with 2-APB treatment. Furthermore, elevated HSP70 formation unexpectedly did not help the cell survival of O. tsutsugamushi-infected macrophages. In conclusion, the parallelism between downregulated Ca2+ mobilization via SOCE and upregulated HSP70 after treatment with 2-APB against TNF-α production was found to efficiently attenuate an O. tsutsugamushi-induced severe inflammatory response.

Background: Staphylococcus aureus (S aureus) is the major cause of skin and soft tissue infections (SSTIs). Increased methicillin-resistant strains have attracted a global concern. The aim of this study is to evaluate the prevalence of methicillin-resistant S aureus (MRSA) SSTIs in dermatologic settings and evaluate their susceptibility results. Methods: A retrospective chart analysis of patients diagnosed with SSTIs in the Department of Dermatology, Buddhist Tzu Chi General Hospital in Hualien, Taiwan from November 2003 to July 2007 was conducted. Wound or pus bacterial culture results from a wound site were collected. The epidemiology, microbiology, and antibiotic susceptibility were assessed. Minocycline treatment experience in 15 MRSA SSTIs inpatients was presented. Results: Of the 443 SSTI episodes included, 59.6% were males and 40.4% were females. S aureus was the leading cause (53.3%), and among them 53.0% were MRSA. Minocycline (94.4%), trimethoprim/sulfamethoxazole (95.2%), levofloxacin (95.7%), and fusidic acid (98.9%) were the major susceptible antimicrobial agents to MRSA. Only 14.4% was susceptible to clindamycin. In the MRSA infected inpatients, 75.6% were community-associated. In our clinical experience, 15 inpatients with poor clinical response to beta-lactam empirical antimicrobial therapy received minocycline as combination therapy based on the susceptibility results, all of which obtained satisfied clinical remission. Conclusions: S aureus is still the leading causative bacterial organism for SSTIs in the dermatologic settings in eastern Taiwan. Methicillin-resistant strains are increasing and among which most are community-associated in eastern Taiwan. MRSA strains are still susceptible to other non-beta lactam antibiotics, such as minocycline, trimethoprim/sulfamethoxazole, levofloxacin, and fusidic acid in dermatological settings, of which minocycline is an alternative choice in our clinical experience.