Citations

Abstract Description Neurons upregulate MHC Class I during infection and neuroinflammation associated with demyelinating diseases, allowing them to present both self and foreign antigens to CD8+ T cells. We hypothesized that ablation of neuronal MHC I expression reduces neural antigen-specific CD8+ T cell recruitment to demyelinated CNS and reduces neuron loss. We have previously shown that demyelination induces expression of MHC Class I on neurons and axons, allowing neuron-specific neoantigens to be presented to CD8+ T cells, leading to neuroinflammatory damage. Elevated MHC-I and β2-microglobulin expression in white and grey matter tissue from MS patients further supported the role of CD8+ T cells in neuronal injury. Here we demonstrate that neuron specific β2-microglobulin ablation in the B6 MOG35-55 EAE model of multiple sclerosis reduces disease progression and severity via clinical scoring. Our preliminary findings suggest that MHC-I ablation may reduce peripheral activation and CNS recruitment of neural antigen-specific CD8+ T cells as well as CD8+ T cell-mediated neurodegeneration in in the context of demyelinating disease. Future studies are aimed at generating a humanized mouse model reconstituted with patient immune cells to understand the role of MHC I expression in neurons, astrocytes, and oligodendrocytes. Specifically, using this model, we will characterize brain infiltrating T cells from patients with CNS autoimmune disease and suspected T cell involvement. Funding Sources Generous donation from Don and Fran Herdrich. Topic Categories Neuroimmunology (NEUR)

AbstractBackground/ObjectivesUlceration is a common complication of infantile hemangioma (IH). Severe, persistent ulceration occurs in a minority of patients. This study aims to characterize the clinical features of IH with aggressive ulceration (AU).MethodsMulticenter retrospective study of clinical features of IH with AU.ResultsThirty‐five patients with AU were identified and included in the study. The majority of AU occurred in segmental IH (23/35, 65%). Segmental IH with AU were large (≥10 cm2; 16/23, 69%, p < .001) with a thin (<3 mm) superficial component (16/23, 69%, p < .001). Localized IH with AU had a thick (>3 mm) superficial component (11/12, 92%, p < .001).All diaper area IH with AU (9/35) were segmental with thin superficial component (100%, p = .02). IH with AU in the head/neck (10/35) were more commonly localized (67%) and mixed (62.5%), while segmental, thick superficial morphology was more common on trunk (9/35) and upper extremities (7/35).ConclusionsIH resulting in AU differ in clinical features by anatomic site. Those in the diaper area are nearly always segmental with thin superficial component, whereas other sites tend to be localized, mixed, with thick superficial component. These distinct phenotypes may prove useful in the clinical setting for physicians to identify patterns of IH ulceration with increased risk of aggressive, persistent ulceration.

AbstractBackgroundLittle is known about skin‐related complications in Klippel–Trenaunay syndrome (KTS), a complex vascular anomaly defined by capillary malformation (CM), venous malformation (VM) ± lymphatic malformation (LM) and limb overgrowth. Reported skin‐related complications of KTS include ulceration, vascular ectasias (blebs), bleeding and infection.ObjectiveTo determine the spectrum, prevalence and predictors of skin‐related complications in KTS.MethodsA retrospective review of 410 patients fulfilling KTS criteria was performed to assess for the presence of skin‐related complications.ResultsSkin‐related complications were present in 45% of patients. Most prevalent were CM‐related complications including blebs, bleeding, thickening (25%), cellulitis (22%) and ulceration (21%). Features positively associated with skin‐related complications were presence of LM (OR 17.17; P < 0.001), VM on the buttocks/perineum/genitalia (OR 1.92; P = 0.009), CM on the feet (OR 1.77; P = 0.039) and male sex (OR 1.63; P = 0.034). Features negatively associated with skin‐related complications were CM on the trunk (OR 0.59; P = 0.029) and tissue hypertrophy of the hands (OR 0.27; P = 0.025).ConclusionSkin‐related complications affect nearly half of patients with KTS. Those with lymphatic involvement or malformation presence in the undergarment area or feet are most at risk.

AbstractBackground/ObjectivesThough maculopapular cutaneous mastocytosis is the most common form of pediatric mastocytosis, it remains unclear which patients will experience severe symptoms. We sought to better define the presentation and the cutaneous and systemic signs and symptoms in patients with maculopapular cutaneous mastocytosis.MethodsWe analyzed retrospective data on 227 patients diagnosed with maculopapular cutaneous mastocytosis prior to age 15 years from five US clinical sites. We collected data on signs, symptoms, age of onset, and laboratory testing.ResultsMedian age of onset of maculopapular cutaneous mastocytosis was 3 months, with 94% of patients presenting prior to age 2 (range 0‐15 years). Patients presenting before age 2 had significantly lower serum tryptase level (P = .019). Greater number of skin lesions (P = .006), number of reported skin signs and symptoms (P < .001), and higher tryptase levels (P < .001) were associated with more systemic symptoms.ConclusionChildren with maculopapular cutaneous mastocytosis, who have greater skin involvement, higher serum tryptase level, and more skin signs and symptoms, are more likely to have systemic symptoms.

Purpose Klippel-Trenaunay syndrome (KTS) is a rare combined vascular malformation composed of capillary malformation, lymphatic and/or venous malformation and limb overgrowth, which commonly affects the extremities. Due to limb involvement, it is not uncommon for these patients to require referral to an orthopaedic surgeon. Herein we reviewed the prevalence of orthopaedic diagnoses in a large cohort of KTS patients and described the associated surgical interventions. Methods Between 1976 and 2012, 410 patients fulfilling strict criteria for KTS were evaluated at a single institution. Patient charts were reviewed for demographic information, details of the clinical evaluation, orthopaedic consultation and surgical interventions. Results A total of 264 of 410 patients (64%) with confirmed KTS required orthopaedic evaluation. Of these 264 patients, 84% had documented limb-length discrepancy. Other common diagnoses included: angular deformities (10%), scoliosis (9%), osteopenia/osteoporosis (7%), pathological fractures (6%), joint contracture (5%), degenerative joint disease (4%) and limb/joint pain (4%). Of the 264 patients evaluated by orthopaedic surgery, 133 patients (50.4%) underwent 169 surgeries. Surgery was most commonly performed for limb-length discrepancy (62%). Multivariable analysis confirmed an orthopaedic condition was more likely in patients with lymphatic malformation (odds ratio (OR) 3.78; p < 0.001), as well as in those with bone and/or soft-tissue hypertrophy of the lower extremity (OR 7.51; p < 0.001) or foot (OR 3.23; p < 0.001). Conclusion Orthopaedic conditions are common in patients with KTS and approximately 50% require surgical intervention. Those with a lymphatic malformation and/or soft-tissue hypertrophy of the lower extremity are more likely to need surgery. Level of Evidence Level IV, Descriptive Case Series