Zoster patients on earth and astronauts in space share similar immunologic profiles.

BACKGROUND: On long-duration spaceflight, most astronauts experience persistent immune dysregulation and the reactivation of latent herpesviruses, including varicella zoster virus (VZV). To understand the clinical risk of these perturbations to astronauts, we paralleled the immunology and virology work-up of astronauts to otherwise healthy terrestrial persons with acute herpes zoster. METHODS: Blood samples from 42 zoster patients - confirmed positive by PCR for VZV DNA in saliva (range from 100 to >285 million copies/mL) were analyzed for peripheral leukocyte distribution, T cell function, and plasma cytokine profiles via multi-parametric flow cytometry and multiplex bead-based immune-array assays. Patient findings were compared to normal value ranges specific for each assay that were defined in-house previously from healthy adult test subjects. RESULTS: Compared to the healthy adult ranges, the zoster patients possess (1) a higher proportion of constitutively activated T-cells, (2) a T-cell population skewed towards a more experienced maturation state, (3) depressed general T-cell function, and (4) a higher concentration of 20 of 22 measured plasma cytokines. DISCUSSION: The pattern of immune dysregulation in zoster patients is similar to that of astronauts during spaceflight who shed VZV DNA in their saliva. Because future deep space exploration missions will be of an unprecedented duration, prolonged immune depression and chronic viral reactivation threaten to manifest overt disease in exploration class astronauts.

Tildrakizumab for Moderate-to-Severe Plaque Psoriasis

Psoriasis is an immune-mediated inflammatory skin condition associated with many comorbidities and poor quality of life. The pathogenesis of psoriasis is complex and involves numerous proinflammatory cytokines. Many biologic therapies have been developed to block the action of these proinflammatory molecules, including inhibitors of tumor necrosis factor (TNF), interleukin (IL)-17, IL-12, and IL-23. IL-23 is composed of two subunits, p19 and p40. The p40 subunit is shared with IL-12, and inhibitors of the p40 subunit can block both IL-12 and IL-23 signaling. Recent advances in the understanding of psoriasis, however, have shown IL-23 to be more important than IL-12 in the pathogenesis of psoriasis. This has led to the development of IL-23p19 antagonists, the newest class of biologics for psoriasis. Here, we will discuss the safety and efficacy of tildrakizumab, a monoclonal antibody targeting IL-23p19.

Hydroxyurea-induced hyperpigmentation with iron deposition.

Hydroxyurea is a chemotherapeutic agent that is used in the treatment of various hematological diseases including chronic myelogenous leukemia, polycythemia vera, and sickle cell anemia. Hydroxyurea is also used to treat psoriasis. Drug-induced hyperpigmentation is a known cutaneous side effect of hydroxyurea along with xerosis, dermal ulcers, and dermatomyositis-like eruptions. Hyperpigmentation has been observed in the oral mucosa, nails, and in a generalized or a diffuse pattern. The mechanism of hyperpigmentation related to hydroxyurea is believed to be correlated with increased melanin. Classically, clinical types of diffuse hyperpigmentation owing to iron deposition in the dermis have been associated with minocycline and not with hydroxyurea. We report a novel case in which hydroxyurea hyperpigmentation is associated with iron deposition.

The efficacy of omalizumab in Cutaneous Mastocytosis: A case series.

BACKGROUND: Mastocytosis describes a heterogeneous group of disorders arising from a clonal proliferation of mast cells. Given the lack of curative treatments for the cutaneous form, there is a significant need for superior therapies. Omalizumab is a recombinant DNA-derived humanized IgG monoclonal antibody that selectively binds to human immunoglobulin E (IgE). It represents a potential treatment for the management of cutaneous mastocytosis, which currently has no standard treatment. METHODS: Two patients were treated with subcutaneous omalizumab 300 mg every 4 weeks. DISCUSSION: Patient 1 experienced 50% reduction in cutaneous infiltration and moderate improvement in pruritus. Patient 2 underwent 90% complete clearance of cutaneous lesions and reported full resolution of pruritus. The median duration of treatment was 24 weeks and time to response was 8 weeks. No significant changes in tryptase levels were observed. Both patients experienced injection site reactions. CONCLUSION: We provide evidence from two cases supporting the efficacy of IgE-mediated therapy in the treatment of cutaneous mastocytosis. Even at a higher-than-standard dose (300 mg vs. 150 mg), the drug was well-tolerated. As we await the results of pivotal clinical trials, omalizumab appears to be a promising treatment option in patients with cutaneous mastocytosis unresponsive to traditional therapies.

Epidemiology of Kaposi sarcoma: review and description of the nonepidemic variant.

Kaposi sarcoma (KS) is a rare angioproliferative tumor whose etiology is associated with human herpesvirus 8 (HHV 8). KS lesions typically involve the skin or mucosal surfaces and are characterized by purplish, red-blue, or brown-black macules, papules, and nodules which are prone to bleeding and ulceration. Definitive diagnosis requires biopsy revealing characteristic angioproliferative features. There are four widely recognized types of KS, which are histologically indistinguishable but differ in epidemiology and prognosis. These include classic, endemic, iatrogenic, and epidemic. KS has been increasingly recognized in a new subgroup of patients: men who have sex with men (MSM) but who are HIV-seronegative human immuodeficiency virus-seronegative and have no identifiable immunodeficiency. This fifth variant of KS, termed nonepidemic KS, resembles classic KS in presentation and prognosis. In this literature review, we report the characteristics of nonepidemic KS based on all published cases and highlight the need for clinicians to recognize this new clinical variant.

Perfluorodecalin-infused patch in picosecond and Q-switched laser-assisted tattoo removal: Safety in Fitzpatrick IV-VI skin types.

BACKGROUND: The topical transparent perfluorodecalin-infused (PFD) silicone patch has been demonstrated to reduce epidermal whitening produced in association with laser-assisted tattoo removal. This optical clearing agent has enabled multiple laser passes to be made in one treatment session. Previous studies using the PFD patch have showed enhanced clearance with picosecond and Q-Switched lasers on blue/black tattoos in Fitzpatrick skin types I-III. We sought to explore the safety and efficacy of using the PFD patch with Q-Switched and picosecond lasers in Fitzpatrick skin types IV-VI. STUDY DESIGN/MATERIALS AND METHOD: A retrospective, single institution chart review was used to assess the safety of treating tattoos using the PFD patch with Q-Switched and picosecond lasers in Fitzpatrick skin types IV-VI. A total of 14 patients, ages 23-66 with Fitzpatrick skin types IV-VI were treated with the PFD patches and liquid PFD using the picosecond (532, 785, and 1064 nm) and the Q-switched Nd:YAG (1064 nm). The treated tattoos contained blue, black, red, green, purple, and pink ink. Patient reported adverse events were evaluated. RESULTS: The PFD patch and liquid PFD were used with the picosecond (532, 785, 1064 nm) and the Q-switched Nd:YAG (1064 nm) lasers to treat tattoos safely in 14 patients with Fitzpatrick skin types IV-VI. Furthermore, the PFD patch was used safely when treating tattoo containing blue, black, red, green, purple and pink ink. Multiple passes were better tolerated in patients when using the PFD patch. No adverse effects were reported. CONCLUSION: Our retrospective chart review supports the safety and efficacy of the PFD patch in protecting the epidermis from thermal injury during laser-assisted tattoo removal of multicolored tattoos in patients with Fitzpatrick skin types IV-VI. Lasers Surg. Med. 51:23-26, 2019. © 2018 Wiley Periodicals, Inc.

AIDS-Associated Malignancies.

Malignancies were one of the earliest recognized manifestations that led to the description of the acquired immune deficiency syndrome (AIDS). The majority of cancers in AIDS patients are associated with coinfection with oncogenic viruses, such as Epstein-Barr virus, human herpesvirus 8, and human papillomavirus, with resulting malignancies occurring secondary to diminished immune surveillance against viruses and virus-infected tumor cells. Over 50% of AIDS lymphomas are associated with Epstein-Barr virus (EBV) and/or HHV8 infection. HHV8-associated diseases include Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). EBV is associated with several malignancies, including Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Coinfection with HIV and HPV is associated with an increased risk of various squamous cell carcinomas of epithelial tissues. HAART has significantly impacted the incidence, management, and prognosis of AIDS-related malignancies. In addition to changing the natural history of HIV infection in regard to incidence and survival, HAART has dramatically decreased the incidence of certain virally mediated HIV-associated malignancies such as KS and primary CNS lymphoma. The beneficial effects of HAART on these tumors are attributed to drug-mediated HIV suppression and immune reconstitution. However, HAART has had a less favorable impact on EBV- and HPV-related malignancies. This chapter presents an overview of HIV-associated malignancies mediated by HHV-8, EBV, and HPV, and reviews the effect of HAART on the epidemiology, presentation, treatment, and outcomes of these cancers.

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus.

In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.

Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Papillomaviruses and Merkel cell polyomavirus.

In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.

Complications associated with intimate body piercings.

Intimate body piercings involving the nipple and genitalia have increased in prevalence in both men and women. Despite this increase, there is a deficiency in the literature regarding the short and long-term complications of body piercings, including an increased risk of infection, malignancy, and structural damage to the associated tissue. Breast abscesses associated with nipple piercing can be mistaken as inflammatory carcinoma. Male genital piercings have been associated with urethral rupture, paraphimosis, urethral obstruction, scar formation, and squamous cell carcinoma, whereas female genital piercings may lead to a higher risk of pregnancy and sexually transmitted infections. There are additional problems related to piercings during pregnancy and thereafter. Nipple piercings can hinder breast feeding by inhibiting the milk letdown reflex, increasing nipple sensitivity, and causing discomfort to the infant. Removal of genital piercings during pregnancy could introduce bacteria into the piercing tract, but retaining the piercings could theoretically hinder childbirth. Prevention of complications is critical. Patients must understand the risks of piercings and disclose relevant medical conditions to the practitioner before the procedure. The piercings should be carried out in a hygienic and sterile manner. Finally, physicians should maintain a non-judgmental attitude to encourage patients to seek medical care for complications.

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis.

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis.

Accelerated tattoo removal with acoustic shock wave therapy in conjunction with a picosecond laser.

BACKGROUND: Conventional tattoo removal consists of single-pass treatments, spaced 7-8 weeks apart, for a total of 7-10 sessions. A major limiting factor of this procedure is the development of cavitation bubbles and vacuoles within the epidermis and dermis that result from the rapid heating of tattoo particles by the laser. While multiple-pass methods using the R20 protocol or the PFD patch enhance tattoo removal through epidermal clearance, they have no effect on deep-intradermal pigment associated vacuoles that arise from treatment with lasers such as the Q-switched laser. METHODS: A 28-year-old female with Fitzpatrick skin Type V presented for treatment of a 6-year-old professional black tattoo on the left ventral wrist. She underwent three treatment sessions at 6-8 week intervals using a commercial 1,064-nm picosecond Nd:YAG laser (PicoWay; Candela, Wayland, MA) and a perfluorodecalin (PFD) patch (Merz; Raleigh, NC). At each treatment session, she received two passes with 1,064-nm, 4-mm spot size, a fluence ranging from 2.8 to 3.2 J/cm2 and a laser repetition rate of 2 Hz. Between laser passes and following the final laser pass, the medial portion of the tattoo was treated with acoustic shock wave therapy (ASWT) using the Zwave device (Zimmer Medizin Systems; Irvine, CA) with 90 mJ, 22 Hz, and 1,200 pulses. RESULTS: After three treatment sessions, there was 80% clearance of the medial portion of the tattoo that received the ASWT compared with 60% clearance of the lateral portion of the tattoo that was treated with the picosecond 1,064-nm Nd:YAG laser and PFD patch alone. In the days following each treatment session, the patient noted consistently less edema, erythema and epidermal crusting on the portion of the tattoo that received the ASWT. CONCLUSION: We report a case of 80% tattoo clearance with ASWT in a patient with Fitzpatrick type V skin compared with 60% clearance with the picosecond 1064-nm Nd:YAG laser and PFD patch alone. The concurrent use of the PFD patch, which facilitated multi-pass treatments, may have also increased tattoo fading in this patient. ASWT may enhance tattoo clearance by increasing lymphatic drainage and increasing metabolic activity in the treated area, thereby accelerating the clearance of dermal pigment vacuoles produced by the picosecond laser and minimizing epidermal side effects such as erythema, edema, and crusting. Lasers Surg. Med. 50:890-892, 2018. © 2018 Wiley Periodicals, Inc.

Bullosis Diabeticorum: A Neglected Bullous Dermatosis.

A 75-year-old African-American man presented with a 3-year history of painless, fluid-filled blisters, for which his primary care physician had treated him with doxycycline, cephalexin, and topical corticosteroids, with no significant improvement. The blisters had ruptured spontaneously and healed with scarring. He denied antecedent trauma. His medical history was remarkable for insulin-dependent type 2 diabetes mellitus, hypertension, hypercholesterolemia, primary cutaneous melanoma status-post excision, and breast cancer status-post mastectomy and chemotherapy. Physical examination revealed nontender bullae, measuring up to 4 cm × 3 cm and containing serous fluid, on the anterior portion of both tibias (Figure 1). The Nikolsky sign was negative. There was no evidence of surrounding inflammation. A biopsy revealed subepidermal bullae formation with sparse inflammatory infiltrate (Figure 2). Direct and indirect immunofluorescence studies were negative for immunoglobulin (Ig) G, IgA, IgM, complement C3, C5b-9, and fibrinogen deposition. Culture of the bullous fluid was negative.

Corrigendum: Complications associated with intimate body piercings.

The original article was published on July15, 2017 and corrected on August 15, 2018.The revised version of the article includes a correction to the spelling of an author. The change appears in the revised online PDF copy of this article.