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Frequently used in the management of hypertension and heart failure, hydralazine is associated with the development of adverse rheumatologic side effects. The authors highlight a unique case of drug-induced lupus and drug-induced anti-neutrophil cytoplasmic antibody (ANCA) vasculitis from hydralazine use in a 50-year-old man with sarcoidosis and hypertension.

Proliferating tricholemmal tumors (PTTs) are rare benign neoplasms that arise from the outer sheath of a hair follicle. Occasionally, these PTTs undergo malignant transformation to become malignant proliferating tricholemmal tumors (MPTTs). Little is known about the molecular alterations, malignant progression, and management of MPTTs. Here, we describe the case of a 58-year-old female that had a widely metastatic MPTT that harbored an activating PIK3CA mutation and was sensitive to the PI3K inhibitor, alpelisib (BYL719). We review the available literature on metastatic MPTT, detail the patient’s course, and present a whole genome analysis of this rare tumor.

Background Intensive studies have failed to identify an etiologic agent in >50% cases of community-acquired pneumonia (CAP). Bacterial pneumonia follows aspiration of recognized bacterial pathogens (RBPs) such as Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus after they have colonize the nasopharynx. We hypothesized that aspiration of normal respiratory flora (NRF) might also cause CAP. Methods We studied 120 patients hospitalized for CAP who provided a high-quality sputum specimen at, or soon after admission, using Gram stain, quantitative sputum culture, bacterial speciation by matrix-assisted laser desorption ionization time-of-flight, and viral polymerase chain reaction. Thresholds for diagnosis of bacterial infection were ≥105 colony-forming units (cfu)/mL sputum for RBPs and ≥106 cfu for NRF. Results Recognized bacterial pathogens were found in 68 of 120 (56.7%) patients; 14 (20.1%) of these had a coinfecting respiratory virus. Normal respiratory flora were found in 31 (25.8%) patients; 10 (32.2%) had a coinfecting respiratory virus. Infection by ≥2 RBPs occurred in 10 cases and by NRF together with RBPs in 13 cases. Among NRF, organisms identified as Streptococcus mitis, which share many genetic features of S pneumoniae, predominated. A respiratory virus alone was found in 16 of 120 (13.3%) patients. Overall, an etiologic diagnosis was established in 95.8% of cases. Conclusions Normal respiratory flora, with or without viral coinfection, appear to have caused one quarter of cases of CAP and may have played a contributory role in an additional 10.8% of cases caused by RBPs. An etiology for CAP was identified in >95% of patients who provided a high-quality sputum at, or soon after, the time of admission., Pneumonia results from aspiration of pathogenic bacteria that colonize the nasopharynx. Using Gram stain, quantitative cultures, and viral PCR in hospitalized patients who provided a valid sputum at admission, we show that normal respiratory flora contribute importantly to community-acquired pneumonia.

Subcutaneous administration is a novel way to deliver antibiotics for an infection, but intolerability has been reported. Evaluating the local tolerability of subcutaneously administered antibiotics is not standardized. The goal of this study was to develop an animal model to assess the subcutaneous administration of ceftriaxone. Sprague-Dawley rats were given daily subcutaneous injections for 12 days. The back of each animal was divided into 4 quadrants, with injections rotating each day among the quadrants. Ceftriaxone (1,000 mg/kg of body weight daily) was given in different concentrations and durations. Normal saline and potassium chloride solutions (2 meq/2 ml) were used as negative and positive controls, respectively. After the treatment course, skin samples were biopsied, and the local inflammatory response was assessed histologically using a semiquantitative scoring system. The histopathology scores were compared using a Kruskal-Wallis test. Injections with potassium chloride resulted in full-thickness skin necrosis with subcutaneous atrophy that was not seen in the saline-injected animals; inflammation of the muscular panniculus was observed, with various degrees of myocyte injury. Serosanguinous cavity formation in the subcutaneous compartment was observed when ceftriaxone (125 mg/ml) was given as a bolus injection, but the extent of the local tissue response was remarkably reduced when the same ceftriaxone dose was given at a lower concentration (25 mg/ml) over 120 min (P = 0.63, compared to saline controls). At a low concentration, ceftriaxone infusion was found to be well tolerated in this animal tissue necrosis model. If validated, the model could be an instrumental platform to evaluate different pharmaceutical formulations for subcutaneous delivery.

BACKGROUND: RhIG is used worldwide to reduce the incidence of alloimmunization to D during pregnancy. We report a case of clinically significant neonatal hemolysis mediated by maternally administered RhIG. CASE REPORT: A 25-year-old, O‐, primigravid mother with a negative antenatal antibody screen delivered a 6-lb 4-oz, blood group A, D+ baby girl at 36.5 weeks’ gestation. Prenatal care included a dose of intramuscular RhIG at 28 weeks’ gestation. At delivery, the newborn was markedly jaundiced with a total bilirubin of 6.3 mg/dL, which reached more than 20 mg/dL after 6 days. The newborn’s lactate dehydrogenase (LDH) was 485 U/L (normal

Background Intensive studies have failed to identify an etiologic agent in >50% of patients (patients) who are hospitalized for community-acquired pneumonia (CAP). Gram stain and culture of sputum samples frequently yield “normal respiratory flora” (NRF). We hypothesized that careful study might (1) increase the yield of recognized pathogens; and (2) show, in some patients, an etiologic role for NRF. Methods We studied a convenience sample of adults hospitalized for CAP at a VA Medical Center if they met four criteria: (1) clinical syndrome consistent with pneumonia; (2) newly recognized pulmonary infiltrate; (3) sputum with > 10 WBC per epithelial cell; and (4) < 18 hours antibiotic treatment. For quantification of bacteria, sputum was liquefied in 2% N-acetyl cysteine and diluted serially. Other studies in nearly all patients included blood cultures, urine for pneumococcal (Spn) and Legionella antigen, procalcitonin, B-natriuretic protein and PCR for 13 respiratory viruses, Mycoplasma and Chlamydia. >106 bacteria/mL and a consistent Gram stain indicated a bacterial cause, positive viral PCR indicated a viral cause, and both indicated coinfection. Results 119 patients met study criteria. Recognized bacterial pathogens alone were identified in 47 (40%) cases led by Spn 17 (14%), Haemophilus 17 (14%) and S. aureus 6 (5%). A virus alone was identified in 17 (15%) and coinfection in 11 (9%). We applied these same criteria for NRF. NRF alone were found in 22 (19%) patients with S. mitis predominating. NRF and a respiratory virus were coinfecting in 10 (8%) patients. In total, with the inclusion of NRF, an etiologic agent was found in 95% of patients. Conclusion Our high yield is attributable to selection criteria. With a good-quality sputum and absent prolonged antibiotics, a bacterial cause for CAP was found in 59% of patients, a viral cause in 15%, and coinfection in 17%. Bacterial CAP due to recognized pathogen follows microaspiration of colonizing bacteria from the upper airways. Aspiration of a sufficient inoculum of so-called NRF, especially in older adults or those with damaged clearance mechanisms, might well do the same. Careful microbiologic study of patients who are able to provide a valid sputum sample before prolonged antibiotics enables a microbiologic diagnosis in nearly all cases and shows a potential etiologic role for NRF in about 20%. Disclosures All authors: No reported disclosures.

Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and seem to be highly active clinically with favorable toxicity profiles. We report on two patients with BRAF V600E–mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multiorgan injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy, and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent. Cancer Immunol Res; 1(6); 373–7. ©2013 AACR.

CD30-positive cutaneous lymphoproliferative disorders, a group of T-cell neoplasms, including lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma, require careful clinicopathologic correlation for diagnosis. An association between LyP and the development of a second hematolymphoid malignancy has been established in the literature. LyP has also been reported with systemic amyloidosis, but no such reports have documented coexisting cutaneous amyloid deposition with LyP to our knowledge. A 66-year-old woman with cutaneous amyloidosis, secondary to multiple myeloma, in remission, presented with erythematous and dark-brown papules involving the right arm, scalp, and torso. Punch biopsy of the arm showed a dermal infiltrate of intermediate-sized lymphocytes, some of which displayed a plasmacytoid morphology and prominent nodular subepidermal amyloid deposition. Punch biopsy of the scalp similarly showed a nonepidermotropic dense dermal infiltrate of intermediate-sized plasmacytoid lymphocytes and multifocal amyloid deposition. Both infiltrates were immunophenotypically CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoproliferative processes. Subsequent studies showed no systemic involvement, and clinical correlation suggested a final diagnosis of LyP. We present this case of LyP, which histologically mimics a B-cell proliferation with a plasmacytoid morphology arising in association with cutaneous amyloidosis to highlight the importance of clinicopathologic correlation, a thorough battery of immunohistochemical studies, and consideration for a second hematologic malignancy arising in the setting of LyP.