A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome.

ABSTRACT: We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, in participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC) ≤0.4 × 103/µL. Participants received once-daily mavorixafor or placebo for 52 weeks. The primary end point was time (hours) above ANC threshold ≥0.5 × 103/µL (TATANC; over 24 hours). Secondary end points included TAT absolute lymphocyte count ≥1.0 × 103/µL (TATALC; over 24 hours); absolute changes in white blood cell (WBC), ANC, and absolute lymphocyte count (ALC) from baseline; annualized infection rate; infection duration; and total infection score (combined infection number/severity). In 31 participants (mavorixafor, n = 14; placebo, n = 17), mavorixafor least squares (LS) mean TATANC was 15.0 hours and 2.8 hours for placebo (P < .001). Mavorixafor LS mean TATALC was 15.8 hours and 4.6 hours for placebo (P < .001). Annualized infection rates were 60% lower with mavorixafor vs placebo (LS mean 1.7 vs 4.2; nominal P = .007), and total infection scores were 40% lower (7.4 [95% confidence interval [CI], 1.6-13.2] vs 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor treatment demonstrated significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity/duration, and was well tolerated. The trial was registered at www.clinicaltrials.gov as #NCT03995108.

Multilevel symmetric neuropathic pruritus (MSNP) presenting as recalcitrant "generalized" pruritus.

BACKGROUND: Chronic itch is a disruptive and disabling condition that can lead to psychological stress and depression. OBJECTIVE: We sought to describe an entity of generalized, symmetric, neuropathic pruritus, which we term "multilevel symmetric neuropathic pruritus," and offer possible explanations accounting for its pathogenesis. METHODS: A case series of 14 patients was evaluated at academic institutions from 2011 to 2015. RESULTS: All patients exhibited detectable degenerative vertebral changes, as seen by spinal x-ray or magnetic resonance imaging. In 12 of 14 (85.7%) subjects, the radiographic imaging abnormalities directly correlated with the distribution of their cutaneous findings. Twelve of 14 (85.7%) patients had cutaneous findings along the C5 to C6 and/or C6 to C7 dermatomal distributions. Eleven of 14 (78.5%) patients were overweight or obese, and 14 of 14 (100%) patients had at least 4 risk factors for the development of atherosclerosis. Twelve of 14 (85.7%) patients noted complete or near complete resolution after treatment with gabapentin (300-1200 mg daily). LIMITATIONS: No healthy age-matched control group without pruritus was investigated. CONCLUSION: A combination of multilevel degenerative disc disease of the spine, spinal nerve root impingement, and/or nerve root traction may play a pivotal role in the cause of multilevel symmetric neuropathic pruritus.

The microsecond 1064 nm Nd:YAG laser as an adjunct to improving surgical scars following Mohs micrographic surgery.

BACKGROUND: Scarring following skin surgery is an unavoidable certainty. Scars resulting from Mohs Micrographic Surgery (MMS) can cause both cosmetic and functional problems. Various lasers have been used to treat scars, but the role of the microsecond pulsed 1064 nanometer neodymium-doped yttrium aluminum garnet (1064 nm Nd:YAG) in treating surgical scars is not well-defined. OBJECTIVE: We aim to examine the clinical application of the 1064 nm Nd:YAG laser in improving surgical scars. METHODS: Ten patients who were unhappy with cosmetic or functional outcomes of their surgical scars following MMS were treated with 1-3 sessions of the 1064 nm Nd:YAG laser to improve their scars. Therapy completion was determined by patient satisfaction with the appearance of their scars and/or resolution of any contractures that formed following surgery. RESULTS: All ten patients were pleased with the improved appearance of their scars. Four patients saw complete resolution of an ectropion or eclabium that formed secondary to scar contractures from MMS. The side effects of laser treatments were limited to 1-2 hours of erythema, and there were no incidences of adverse effects or recurrence of contractures. CONCLUSION: Our clinical experience with the 1064 nm Nd:YAG laser provides promising data on improving appearance of and functionality from post-surgical scars.

Voriconazole-Induced Subacute Cutaneous Lupus Erythematosus in an Adult With Aspergillosis.

A 59-year-old man was treated with voriconazole for chronic invasive aspergillosis and who subsequently developed subacute cutaneous lupus erythematosus (SCLE). The patient presented with a 6-week history of multiple erythematous papulosquamous lesions on his chest, upper and lower extremities, and back (Figure 1). They were nonpruritic and nonpainful. He was afebrile and otherwise well. He had no history of extensive sun exposure prior to the appearance of the eruption. He had been taking voriconazole for about 3 months prior to the onset of lesions. He denied any family history of connective tissue disease.

Congenital agminated segmental nevi of the chest.

Grouped patterns of pigmented lesions are infrequent. Of the several reports of agminated nevi, most have been Spitz nevi or blue nevi. The distribution of these nevi is often segmental, following a dermatome or the lines of Blaschko. Most segmental nevi are not agminated and develop early in childhood [1]. We describe a rare case of congenital agminated segmental nevi on the chest.

Dehydrated human amnion/chorion membrane allograft for postoperative wounds following Mohs micrographic surgery: a retrospective comparative evaluation.

INTRODUCTION: Defects that remain after MMS cannot always be repaired immediately. When closure is not feasible, wounds are left to heal by secondary intention and may take weeks to close. In such cases, the use of an allograft that stimulates endogenous wound healing pathways may be desirable. OBJECTIVE: This retrospective study assessed whether the use of dHACM allograft after MMS led to a statistically significant improvement in post-Mohs wound closure rates compared with secondary intention healing. METHODS: This study evaluated 80 patients who underwent MMS and compared time to complete healing between wounds treated with dHACM allografts (n = 40) and wounds healed by secondary intention (n = 40). Wounds were assessed every 2 weeks, and photographs were taken. Statistical analysis was conducted. RESULTS: Average time to complete wound healing was significantly reduced with the use of dHACM allograft compared with traditional secondary intention healing (5.2 weeks and 6.5 weeks, respectively; P = .01). CONCLUSION: The use of dHACM allograft resulted in more rapid wound healing, and this allograft is a potential alternative to traditional secondary intention healing methods. Further studies are needed to reinforce the results of this pilot study.

Central serous chorioretinopathy associated with topical corticosteroids in a patient with psoriasis.

BACKGROUND: Central serous chorioretinopathy (CSC), also known as central serous retinopathy (CSR), is a visual impairment, often temporary, usually in a single eye, which mostly affects males in the age group of 20 to 50 but may also affect women. CSC occurring after prolonged use of topical steroids in a patient with psoriasis is a novel complication in the English literature. OBSERVATIONS: We describe a case of a 25-year-old male, with a 15-year history of corticoid ointment use for psoriasis, who presented with loss of vision secondary to CSR. CONCLUSIONS: All topical steroid treatments were discontinued and the patient recovered his vision completely. Although topical corticosteroids are frequently utilized for psoriasis management with a low rate of complication, clinicians should be familiar with this rare yet distressing condition. Furthermore, patients with increased production of endogenous corticosteroids (e.g., those with Cushing's syndrome, hypertension, or obstructive sleep apnea) should be warned of the potential of chorioretinopathy following prolonged use of topical corticosteroids.

Granuloma annulare in a zoster scar of a patient with multiple myeloma.

Granuloma annulare (GA) is a common benign inflammatory skin disorder with an unknown pathogenesis. Granuloma annulare occurring in prior sites of herpes zoster (HZ) infection is rarely reported; however, it is the most common granulomatous reaction described at these sites. We report a case of localized GA on scars of prior HZ infection in a patient with multiple myeloma who had received an autologous peripheral stem cell transplant (PSCT). This patient's GA was successfully treated with intralesional corticosteroid injections.

Hereditary multiple exostoses with spine involvement in a 4-year-old boy.

Hereditary multiple exostosis (HME) is an autosomal dominant disorder characterized by multiple osteochondromas. We describe a case of acute cervical spinal cord compression arising from an exostosis at the lamina of C7 and T1 in a 4-year-old Mexican-American boy with HME. His affected sibling also displayed spinal cord compression because of a bony exostosis. Acute cervical spinal cord compression resulting from osteochondroma is a serious complication of HME. (c) 2010 Wiley-Liss, Inc.

CD30 positive anaplastic large-cell lymphoma mimicking Langerhans cell histiocytosis.

The presence of CD 1a+ dendritic cells (DC) has been well described in T-cell lymphoproliferative disorders, and the presence of large numbers of DCs has rarely been reported as a mimicker of Langerhans cell histiocytsis (LCH). We present the case of a 56-year-old female with a solitary nodule on the chin whose case was referred to our institution for confirmation of the diagnosis of LCH. Skin biopsy showed an ulcerated nodule containing a wedge-shaped infiltrate comprised of large atypical cells and cells with prominent grooved nuclei. The constellation of histologic and immunologic features favored a CD30 lymphoproliferative disorder of T-cell lineage even though there were accompanying numerous dendritic histiocytes and CD1a positive Langerhans cells. The sheets of CD30 positive atypical lymphoid cells which express T-cell markers were consistent with CD30 positive lymphoproliferative disease and favor CD30 positive anaplastic large-cell lymphoma (ALCL) over Langerhans histiocytosis. The absence of Anaplastic Lymphoma Kinase (ALK) staining favored a primary cutaneous origin. This case signifies a CD 30+ ALCL of the skin which histopathologically mimics a LCH. Ezra N, Van Dyke GS, Binder SW. CD30 positive anaplastic large-cell lymphoma (ALCL) mimicking Langerhans cell histiocytosis (LCH).

CTLA4-induced splenomegaly and a review of the literature pertaining to autoimmune complications of therapy.

CTLA4-blocking antibodies induce tumor regression in a subset of patients with metastatic melanoma by optimizing T-cell activity to fight the malignant cells. In addition to therapeutic benefits, CTLA4 therapy may induce immune-related adverse events (irAE). Studies on CTLA4 knockout and other CTLA4 deficient mice have resulted in splenomegaly, lymphoproliferation and fatal multi-organ destruction. The authors present a case of a 68-year-old patient who has developed splenomegaly following CTLA4 therapy. CTLA4 therapy's risks and benefits should be weighed carefully in the treatment of malignant melanoma. Larger prospective multi-center trials are needed to gauge the efficacy and complication rate of CTLA4 therapy. The authors propose that patients should get short-term surveillance imaging (CT or PET/CT) to exclude the multiple abdominopelvic complications and quickly terminate therapy if clinically warranted. It is also necessary for clinicians to carefully monitor for the number of possible complications associated with this immunotherapy.

The advent of a novel diagnosis: melanoma through the ages.

In the 1930s, the risk of contracting melanoma was only 1:1500; however, by 1996 this number had risen to 1:87 and has been increasing ever since. To better understand the nature of melanoma, books, journals, and scholarly literary works were searched and contributors of this disease were studied in greater detail. Antiquity of melanoma is said to be approximately 2400 years old based on observations made on 9 Peruvian Inca mummies in the 1960s that showed apparent signs of melanoma. René Théophile Hyacinthe Laënnec, the inventor of the stethoscope, first described melanoma as a disease entity. William Norris, an English general practitioner, gave the first English language report of this disease. There are many other physicians from France, England, and the United States who had an active role in the discovery of melanoma.

Pelvic and scrotal trauma: CT and triage of patients.

Traumatic dislocation of the testicles was first reported during crush injury but is now more commonly related to motor vehicle accidents. Approximately 55 cases had been reported by 2003. Virtually no papers discuss the role of CT in the rapid diagnosis of penoscrotal trauma, although most polytrauma or "pelvic trauma" patients are rapidly evaluated by CT in the emergency room setting. As more patients with pelvic trauma are triaged and evaluated using CT scanners with greater multidetector capability, more patients will be seen with testicular injury. It is important for the emergency physicians, radiologists, and traumatologists not to overlook unsuspected cases of penoscrotal injury which are typically initially evaluated by history, physical exam, and ultrasound. We describe a recent case of initial diagnosis of bilateral testicular dislocation from blunt trauma using modern multidetector CT imaging technique.

Multiple keratoacanthomas occurring in surgical margins and de novo treated with intralesional methotrexate.

Keratoacanthomas (KAs) are common skin lesions known for their rapid growth and spontaneous regression. Keratoacanthomas also can occur in sites of prior trauma, such as surgical scars. We report a case of multiple KAs occurring in the site of trauma from a prior surgery and de novo as well as the response to treatment with intralesional methotrexate (MTX).

Linear scarring following treatment with a 595-nm pulsed dye laser.

Pulsed dye laser (PDL) treatment is well established and has been reported to be safe and effective in the management of superficial hemangiomas, port-wine stains, and other vascular lesions. Although hyperpigmentation is quite common, other side effects such as hypopigmentation, ulceration, hemorrhaging, atrophic scarring, and hypertrophic scarring are rare. We report the case of a 42-year-old woman who developed atrophic scarring of the nasal alae following cosmetic PDL treatment. Patients receiving PDL treatment should be warned about the risk for the development of scarring.