A case of certolizumab-induced purpura annularis telangiectodes of Majocchi and literature review.

Tumor necrosis factor alpha (TNFα) inhibitors are now widely used to treat immune-mediated inflammatory diseases. Although they have a good safety profile, they are also associated with adverse cutaneous events. Pigmented purpuric dermatoses (PPD) include a variety of skin diseases characterized by multiple petechial hemorrhages due to capillaritis. Five major clinical types of PPD have been described and purpura annularis telangiectodes of Majocchi (PATM) is a rare subtype of PPD. The cause of PPD is unknown, but drugs are implicated in a minority of cases. There are very few cases in the literature triggered by TNFα inhibitors. We present a case of PATM induced by certolizumab pegol and perform a review including 4 articles in the literature reporting 5 PPD cases induced by TNFα inhibitors. When purpuric eruptions develop in patients treated with TNFα inhibitors, PPD and vasculitis should be differentiated. Thus, patients are not exposed to unnecessary evaluations and treatments.

A Rare Skin Rash: Linezolid-Induced Purpuric Drug Eruption without Vasculitis in a Puerto Rican Man.

BACKGROUND Cutaneous adverse drug reactions are the skin's response to a systemic exposure to drugs. Linezolid is an oral oxazolidine used to treat methicillin-resistant Staphylococcus aureus infections. Even though it has well-known adverse effects, purpuric cutaneous adverse drug reactions to linezolid have been scarcely described. This report is of a Puerto Rican man in his 80s who developed an extensive purpuric drug eruption secondary to linezolid use. Clinicians should be aware of this phenomenon, since prompt identification and discontinuation of the agent are essential for recovery. CASE REPORT An 89-year-old Puerto Rican man was given oral linezolid therapy for healthcare-associated pneumonia and developed a widespread, purpuric cutaneous eruption 5 days into therapy. His condition prompted immediate discontinuation of the drug. Forty-eight hours after stopping the medication, he visited the Emergency Department. Abdominal punch biopsy revealed a superficial and perivascular lymphocytic infiltrate with dermal eosinophils, a pathologic finding consistent with a purpuric drug eruption. This allowed for a timely diagnosis, exclusion of other mimickers, such as cutaneous vasculitis, and effective management. CONCLUSIONS Cutaneous adverse drug reactions to linezolid have been scarcely reported in the literature. Due to the low incidence of this manifestation, the identification of the causative agent and accompanying treatment may be delayed. Mainstays in therapy are avoidance of the offending agent and treatment with corticosteroids, antihistamines, barrier ointments, and oral analgesics. Primary healthcare providers should be aware of linezolid-induced cutaneous manifestations, diagnostic clues, and treatment options so they can rapidly identify and effectively treat such complications.

Blood-conserving and therapeutic efficacy of intravenous tranexamic acid at different time points after primary total knee arthroplasty with tourniquet application: a randomised controlled trial.

BACKGROUND: The use of a tourniquet in combination with tranexamic acid (TXA) not only ensures clear vision, reduces intraoperative blood loss and shortens operative time but also improves cement-bone inter-digitation in total knee arthroplasty (TKA). However, there is no proof whether the blood flow blocking effect of tourniquet affects the antifibrinolytic effect of TXA, and the optimal timing of TXA administration is still unclear. Therefore, this study aims to investigate the effect of the first dose of TXA administered intravenously before tourniquet compression and release in TKA on perioperative blood loss and therapeutic efficacy in patients. METHODS: In this double-blind trial, 90 patients undergoing primary TKA were randomised into 2 groups: Group A, patients received intravenous TXA 10 min before tourniquet compression (20 mg/kg) and 3, 6 and 24 h later (10 mg/kg), and Group B, patients were treated the same as those in Group A but received intravenous TXA before tourniquet release. The primary outcomes were changes in blood loss, haemoglobin and haematocrit. Secondary outcomes included operation and tourniquet times, blood transfusion rate, subcutaneous petechiae and circumferential changes in the operated limb, visual analogue scale (VAS) score, hospital for special surgery (HSS) score, length of stay (LOS) postoperatively, complications and patient satisfaction. RESULTS: No statistically significant difference was found between the 2 groups with regard to age, sex, weight, body mass index (BMI), Kellgren-Lawrence class, preoperative blood volume, preoperative laboratory values, operation and tourniquet times, transfusion rate, knee circumference, preoperative HSS, or VAS score (P:n.s.). There was no significant difference in intraoperative blood loss (IBL) (52.7 ml vs. 63.4 ml, P = 0.07), hidden blood loss (HBL) (91.4 ml vs. 119.9, P = 0.4) or total blood loss (TBL) (144.1 ml vs. 183.3 ml, P = 0.72) between Groups A and B. Haemoglobin, haematocrit and red blood cell count (RBC) dropped to a low point on postoperative day 3 and then rebounded, returning to normal levels on day 21, and the trend of change between the 2 groups was not statistically significant (P:n.s.). There was no significant difference in subcutaneous ecchymosis incidence, knee swelling rate, HSS score, VAS score, LOS postoperatively, complication rate or patient satisfaction (P:n.s.). CONCLUSION: TXA was administered intravenously prior to tourniquet compression could effectively reduce blood loss in patients who had undergone total knee arthroplasty. However, there was no significant difference in knee swelling rate, subcutaneous bruising and petechiae incidence, knee function, complication rate or satisfaction between patients who TXA was given intravenously before tourniquet compression and release in primary TKA.

Angiokeratoma-like purpuric palmar nodules following chemotherapy.

We describe a patient with leukemia undergoing chemotherapy who developed painful purpuric nodules of the digits. These findings were concerning for endocarditis (clinically) and angiokeratomas on gross histology. After extensive evaluation, we report the development of painful purpuric nodules as a likely side effect of the patient's therapeutic regimen (hydroxyurea, danorubicin, cytarabine, and methotrexate).

Safety and antitumor activity of acalabrutinib for relapsed/refractory B-cell malignancies: A Japanese phase I study.

This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.

Cutaneous Polymer-Coating Embolism After Endovascular Procedures: Report of Two Cases and a Literature Review.

ABSTRACT: Different hydrophilic and hydrophobic polymers are used as lubricious coatings to reduce vascular traumas in minimally invasive percutaneous procedures. Although they are usually very safe, there is still a risk of serious complications in patients undergoing such procedures, mostly derived from the devices' coating detachment and systemic embolization. The lungs are the most common organ involved, followed by the central nervous system. Yet, cutaneous embolization is unusual, and only 19 cases are available in the literature. Most commonly, they present as asymptomatic retiform purpura on the lower legs, which tends to involve spontaneously. Correct clinical diagnosis is not suspected in most cases, being cholesterol emboly or vasculitis the preferred options. Time interval since surgical procedure and appearance of lesions vary widely but they generally start in the first few days. Histopathological identification of the embolus as bluish, amorphous intraluminal material in dermal vessels is diagnostic, but vasculitic signs are not present. We report 2 cases of skin lesions as the main manifestation of polymer embolization after endovascular surgical procedures. In both cases, biopsy allowed identification of embolized foreign material and lesions resolved without specific treatment.

Intermittent Purpura Development Associated with Leukocytoclastic Vasculitis Induced by Infliximab for Crohn's Disease.

Anti-tumor necrosis factor (TNF) α agents, widely used for the treatment of Crohn's disease (CD), can sometimes induce skin-associated adverse events, which mainly include psoriasis-like eruptions, eczema, and cutaneous infections. In contrast, purpura caused by vasculitis is rarely seen. We herein report a unique case of leukocytoclastic vasculitis induced by infliximab administered for CD in which intermittent purpura development was noted. Fluorescent immunostaining showed no immunoglobulin A deposition on the vessel walls. No purpura was initially seen after starting infliximab, but it appeared approximately 10 months later; however, administration did not have to be discontinued, and the condition was later resolved. The present findings provide important details regarding vasculitis induced by anti-tumor necrosis factor-α agent administration.

Hairy cell leukaemia diagnosed in a polysensitized patient with atypical haemorrhagic skin lesions / Atípusos haemorrhagiás bortünetek hátterében igazolt hajas sejtes leukaemia poliszenzibilizált betegen.

As the topical use of non-steroidal anti-inflammatory drugs (NSAIDs) has gained popularity recently, adverse reactions related to their application have also become more common. The authors present the case of a 49-year-old man, who used etofenamate gel to treat leg pain. Following sun exposure, haemorrhagic, atypical lesions appeared and after rapid spread of the symptoms, the patient was hospitalized. In the area of the etofenamate application as well as on both legs, arms, trunk and face, confluent, erythematous sero-papules and macules were found, along with petechiae on the oral mucosa. Splenomegaly and thrombocytopenia accompanied the skin symptoms, which prompted an oncohematological workup, and the patient was diagnosed with hairy cell leukaemia. Epicutaneous testing (ET) was performed and found a positive reaction to etofenamate gel as well wood tar, propylen glycol, fragrance mix I, methylisothiazolinone, benzoic acid and balsam of Peru. The lymphocyte transformation test (LTT) and CD69 expression were negative for etofenamate. Orv Hetil. 2020; 161(38): 1646-1651.

Bevacizumab-induced immunoglobulin A vasculitis with nephritis: A case report.

RATIONALE: Bevacizumab-an inhibitor of vascular endothelial growth factor-is effective against various advanced cancers. However, it is associated with the development of hypertension and high-grade proteinuria during thrombotic microangiopathy of the kidney. In addition, there are several reports of immunoglobulin A deposition in the glomeruli, but the etiology is unclear. PATIENT CONCERNS: A 67-year-old Japanese man with metastatic rectal cancer underwent low anterior rectal resection, followed by treatment with bevacizumab and SOX (S-1 plus oxaliplatin). Six months later, the patient developed hematuria, nephrotic syndrome, and purpura. DIAGNOSES: Renal biopsy revealed endocapillary proliferative glomerulonephritis. Immunofluorescence analyses showed granular mesangial deposition of galactose-deficient immunoglobulin A1. Skin biopsy revealed leukocytoclastic vasculitis. INTERVENTIONS: We ceased bevacizumab treatment, while continuing the remaining chemotherapy regimen, as we suspected bevacizumab-induced nephropathy. OUTCOMES: Proteinuria and purpura improved immediately after cessation of bevacizumab. We identified this as a case of bevacizumab-induced immunoglobulin A vasculitis with nephritis. LESSONS: To our knowledge, this is the first case of bevacizumab-related immunoglobulin A vasculitis with nephritis, as evidenced by galactose-deficient immunoglobulin A1. When a patient's urine tests are abnormal during bevacizumab treatment, clinicians should consider not only thrombotic microangiopathy but also vasculitis.

Leukocytoclastic vasculitis with purpura and renal failure induced by the anti-epidermal growth factor receptor antibody panitumumab: a case report.

BACKGROUND: Panitumumab is the first human combinatorial antibody for the treatment of metastatic colorectal carcinoma. Dermatologic toxicity of all grades occurs in more than 90% of patients. However, there are few reports of purpura induced by anti-epidermal growth factor receptor antibody. Renal failure is also uncommon as an adverse event of anti-epidermal growth factor receptor antibody. CASE PRESENTATION: A 67-year-old Japanese man with advanced colon cancer received monotherapy with panitumumab. General malaise, bilateral edema of his legs, and bilateral purpura of his forearms developed 2 days after the second cycle of panitumumab. A skin biopsy was performed to evaluate the purpuric lesions on his left leg and leukocytoclastic vasculitis was diagnosed. Blood tests showed grade III acute renal failure with a blood urea nitrogen level of 33.8 mg/dL and a creatinine level of 3.10 mg/dL. CONCLUSIONS: This is the first reported case of leukocytoclastic vasculitis followed by purpura and acute renal failure associated with panitumumab.

Levamisole-induced vasculopathy with gastric involvement in a cocaine user.

Reports of levamisole-induced vasculopathy (LIV) secondary to use of levamisole-contaminated cocaine largely have been limited to the skin. We report the case of a 35-year-old woman with painful purpuric lesions affecting the cheeks, nose, ears, arms, and legs of several days' duration. She recently had used crack cocaine. A biopsy of a lesion on the right arm demonstrated leukocytoclastic vasculitis. She also reported abdominal pain and gastric reflux of recent onset but denied any history of gastrointestinal tract disease. An upper gastrointestinal endoscopy was performed and demonstrated hemorrhagic erosions of the esophagus and stomach similar in appearance to the cutaneous lesions. Because dermatologists often are the specialists making the diagnosis of LIV, it is important they inform other involved clinicians that the skin may not be the sole repository of vascular insult.

Paraneoplastic IgA Vasculitis in an Adult with Lung Adenocarcinoma.

A 50-year-old man with lung adenocarcinoma (c-T1aN2M1b) experienced reddish purpura mainly on the lower legs after receiving 12 cycles of second-line chemotherapy with docetaxel. There was tumor enlargement on computed tomography performed to assess the therapeutic response, so paraneoplastic IgA vasculitis was considered. IgA vasculitis was diagnosed based on a biopsy of the skin lesion and histology of an upper gastrointestinal hemorrhagic mucosal erosion. As IgA vasculitis can lead to serious gastrointestinal or systemic complications, IgA vasculitis should be considered as a differential diagnosis for rashes in patients with malignancy.

Bioenergetics dysfunction, mitochondrial permeability transition pore opening and lipid peroxidation induced by hydrogen sulfide as relevant pathomechanisms underlying the neurological dysfunction characteristic of ethylmalonic encephalopathy.

Hydrogen sulfide (sulfide) accumulates at high levels in brain of patients with ethylmalonic encephalopathy (EE). In the present study, we evaluated whether sulfide could disturb energy and redox homeostasis, and induce mitochondrial permeability transition (mPT) pore opening in rat brain aiming to better clarify the neuropathophysiology of EE. Sulfide decreased the activities of citrate synthase and aconitase in rat cerebral cortex mitochondria, and of creatine kinase (CK) in rat cerebral cortex, striatum and hippocampus supernatants. Glutathione prevented sulfide-induced CK activity decrease in the cerebral cortex. Sulfide also diminished mitochondrial respiration in cerebral cortex homogenates, and dissipated mitochondrial membrane potential (ΔΨm) and induced swelling in the presence of calcium in brain mitochondria. Alterations in ΔΨm and swelling caused by sulfide were prevented by the combination of ADP and cyclosporine A, and by ruthenium red, indicating the involvement of mPT in these effects. Furthermore, sulfide increased the levels of malondialdehyde in cerebral cortex supernatants, which was prevented by resveratrol and attenuated by glutathione, and of thiol groups in a medium devoid of brain samples. Finally, we verified that sulfide did not alter cell viability and DCFH oxidation in cerebral cortex slices, primary cortical astrocyte cultures and SH-SY5Y cells. Our data provide evidence that bioenergetics disturbance and lipid peroxidation along with mPT pore opening are involved in the pathophysiology of brain damage observed in EE.

Linear atrophy and vascular fragility following ultrasoundguided triamcinolone injection for DeQuervain tendonitis.

A 64 year-old woman presented with a one-yearhistory of purpuric, atrophic, linear patches alongthe left lateral forearm. The patient had receivedtwo ultrasound-guided triamcinolone injectionsone year earlier into her left extensor pollicis brevisand abductor pollicis longus tendon sheathsfor DeQuervain tendonitis. In the seven monthsfollowing the second injection, the patient developedatrophy, purpura, and telangiectasias starting at thesite of injection and extending proximally, followingthe course of her left cephalic vein. The patient wastreated initially with amlactin and moisturizing creamcontaining alpha-hydroxy acid cream to aid in dermalrepair. Despite treatment, she continued to haveproximal progression of the atrophy and purpura.A 4mm punch biopsy revealed a normal-appearingepidermis overlying horizontal dermal fibrosis, alongwith atrophic-appearing adipocytes with accentuatedcapillaries in the subcutaneous fat, consistent witha diagnosis of corticosteroid atrophy. These grossand microscopic changes presumably resulted fromlymphatic uptake and spread of the corticosteroidfollowing the injections for tendonitis. Although localatrophy and vascular fragility are well-documentedside effects of corticosteroid injections, linear spreadof these symptoms is rarely reported, and to this pointhas not been demonstrated in the literature followingultrasound-guided steroid injection for DeQuervaintendonitis.

ANCA Associated Vasculitis Secondary to Levamisole-Adultered Cocaine with Associated Membranous Nephropathy: A Case Series.

BACKGROUND: Cocaine is a risk factor for acute kidney injury and chronic kidney disease with progression to end-stage renal disease. Levamisole is an adulterant that is added to cocaine to enhance its euphoric effects. Levamisole-adulterated cocaine (LAC) is associated with the distinct clinical syndromes of agranulocytosis, leukocytoclastic vasculitis, cocaine-induced midline destructive lesions (CIMDL), and ANCA-associated vasculitis (AAV) with pauci-immune necrotizing glomerulonephritis. METHODS: We reviewed all cases of AAV secondary to LAC at our institution. RESULTS: We report 3 cases of AAV secondary to LAC and associated membranous nephropathy (MN). The first and second cases are concurrent AAV secondary to LAC and associated MN while the third case involves the development of MN after AAV secondary to LAC. CONCLUSIONS: Clinicians should be aware of this novel association of LAC with MN.

Prednisone and vardenafil hydrochloride for refractory levamisole-induced vasculitis.

Levamisole is an immunomodulatory drug that was previously used to treat various medical conditions, including parasitic infections, nephrotic syndrome, and colorectal cancer. Over the last few years, increasing amounts of levamisole have been used as an adulterant in cocaine. Levamisole-cut cocaine has become a concern because it is known to cause a necrotizing purpuric rash, autoantibody production, and life-threatening leukopenia. Mixed histologic findings of vasculitis and thrombosis are characteristic of levamisole-induced purpura. The recommended management of levamisole-induced vasculitis currently involves withdrawal of the culprit along with supportive treatment. We describe a patient with levamisole-induced vasculitis who continued to develop skin lesions despite self-reported cocaine cessation. Complete resolution of cutaneous disease occurred with the addition of oral prednisone and vardenafil hydrochloride, suggesting the possibility of a new treatment option in patients with refractory disease. In addition, we review the clinical presentation, disease course, diagnostic approach, laboratory findings, histology, and management of levamisole-induced vasculitis. The harmful effects of levamisole-cut cocaine are serious enough that public alerts have been issued to increase awareness. Clinicians should consider the possibility of levamisole exposure in cocaine users presenting with any combination of fever, neutropenia, and necrotic skin lesions, especially in acral areas including the ears.

Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.