Recurrent Purpura Research Articles

Associations of MEFV gene variants, IL-33, and sST2 with the risk of Henoch-Schönlein purpura in children

ObjectiveHenoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. HSP is a multifactorial inflammatory disease, but its pathogenesis is still unclear. The pathogenicity of familial Mediterranean fever gene (MEFV) variants in HSP remains controversial. The objective of this study was to evaluate relationships between MEFV variants and susceptibility to HSP and their associations with clinical outcomes. We also investigated levels of IL-33 and soluble suppression of tumorigenicity 2 (sST2) in children with HSP and their clinical significance. MethodsWe selected 100 children with HSP as the case group. The control group consisted of 50 children who visited the hospital for physical health examinations. All subjects were screened for MEFV gene exon mutations, and levels of IL-33 and sST2 were measured. ResultsThe frequency of MEFV variants was significantly greater in HSP patients than in healthy controls. The variant with the highest frequency was E148Q. The frequency of the C allele of the MEFV variant E148Q was 32 % in HSP patients and 18 % in controls (P-adjust = 0.04). Patients with the MEFV E148Q variant had more frequent joint involvement and recurrent purpura and higher levels of IL-33 and C-reactive protein (CRP). Levels of IL-33 and sST2 in children with HSP were significantly higher than those in the control group, and the sST2/IL-33 ratio in children with HSP was unbalanced (P-adjust <0.05). Logistic regression analysis revealed the presence of E148Q and an unbalanced sST2/IL-33 ratio to be independent risk factors for HSP. ConclusionThe results of this study suggest that the MEFV variant E148Q is associated with HSP susceptibility in Chinese children and that carriers of the variant may have more severe clinical manifestations and greater inflammatory responses. E148Q and the sST2/IL-33 ratio may play important roles in the pathogenesis of HSP.

A Different Approach in a Case of Recurrent Purpura

A Different Approach in a Case of Recurrent Purpura

Prediction of renal damage in children with IgA vasculitis based on machine learning.

This article is objected to explore the value of machine learning algorithm in predicting the risk of renal damage in children with IgA vasculitis by constructing a predictive model and analyzing the related risk factors of IgA vasculitis Nephritis in children. Case data of 288 hospitalized children with IgA vasculitis from November 2018 to October 2021 were collected. The data included 42 indicators such as demographic characteristics, clinical symptoms and laboratory tests, etc. Univariate feature selection was used for feature extraction, and logistic regression, support vector machine (SVM), decision tree and random forest (RF) algorithms were used separately for classification prediction. Lastly, the performance of four algorithms is compared using accuracy rate, recall rate and AUC. The accuracy rate, recall rate and AUC of the established RF model were 0.83, 0.86 and 0.91 respectively, which were higher than 0.74, 0.80 and 0.89 of the logistic regression model; higher than 0.70, 0.80 and 0.89 of SVM model; higher than 0.74, 0.80 and 0.81 of the decision tree model. The top 10 important features provided by RF model are: Persistent purpura ≥4 weeks, Cr, Clinic time, ALB, WBC, TC, Relapse, TG, Recurrent purpura and EB-DNA. The model based on RF algorithm has better performance in the prediction of children with IgA vasculitis renal damage, indicated by better classification accuracy, better classification effect and better generalization performance.

Unusual purpura as a first sign of amyloid light chain amyloidosis.

A 48-year-old woman presented to our hospital in February, 2021, with a 1-year history of recurrent purpura after minor scratching, especially on the periorbital and perianal areas. She also reported that she had been experiencing intermittent haemorrhagic blisters on her tongue. She denied any other unusual clinical symptoms and her medical history was otherwise unremarkable. On physical examination, petechiae less than 5 mm in size were noted on the perinasal areas, neck, and armpit (figure). Systemic check-up, including examination of the tongue, did not show any other notable findings. Purpura on the perinasal areas (A) and neck (B).

Erythromelalgia presenting as recurrent purpura and hypogammaglobulinemia: A case report

Erythromelalgia presenting as recurrent purpura and hypogammaglobulinemia: A case report

Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals.

Hepatitis C virus (HCV) infection is responsible for both hepatic and extrahepatic manifestations. Before the era of direct-acting antivirals (DAA), cryoglobulinemia was related to HCV infection in 70–90% of cases. Observed in 30% to 40% of patients with hepatitis C, mixed cryoglobulinemia is mainly asymptomatic. Conversely, symptomatic cryoglobulinemia vasculitis (CV) can occur in 5–10% of patients with HCV-associated cryoglobulinemia. CV is a small-vessel systemic vasculitis, and organ damage results from circulation and precipitation of cryoglobulins and complement activation. A wide range of clinical symptoms can be observed during CV, and manifestations are potentially life-threatening. The most frequent manifestations occurring in CV are cutaneous, with recurrent purpura, articular with joint pains, neurologic with peripheric neuropathy, and renal with membranoproliferative glomerulonephritis. DAA have drastically changed chronic HCV therapy. DAA induce sustained virological response (SVR) rates greater than 95%, and also improve extrahepatic manifestations such as CV. We review recent studies investigating the clinical and immune effects of DAA therapy on HCV-CV.

Diagnosis and management of early-onset thrombophilia/thrombosis: a review

Evidence of the molecular epidemiology of thrombophilia is growing, and the clinical management of adult thromboembolism patients has recently made significant progress. On the other hand, there is little or no evidence concerning the genetic variation, treatment, and prophylaxis of thromboembolism development in the early life stage. The clinical presentation of early-onset thrombosis/thrombophilia, which mostly occurs in newborns and adolescents, differs from that in cases of adult-onset. Recurrent purpura fulminans and/or intracranial hemorrhage/infarction leads to dangerous lifelong complications. As in the setting of cancer genomic medicine, germline variants require determination for the individualized control of early-onset thrombophilia. The genetic predisposition to thrombosis varies among ethnicities. In the Japanese population, the protein S variant (PS-Tokushima, K196E) has attracted attention as the cause of a common and low-risk prothrombotic predisposition in adults, while protein C deficiency greatly impacts the onset of pediatric thrombosis. In 2020, 3 years after the registration of idiopathic thrombosis as a designated intractable disease, genetic tests have been promulgated for health insurance portability. Disease-specific therapy for early-onset thrombophilia is crucial. Here, we review the genetic heterogeneity, prophylaxis, and treatment strategy of the rare subgroups of severe heritable thrombosis conditions in Japan.

Case 1: A Rare Case of Antenatal Hemorrhagic Stroke and Recurrent Purpura Fulminans in a Preterm Newborn

A female infant is born prematurely at 33 weeks of gestation to consanguineous parents (parents are first cousins). The mother has had 2 uneventful pregnancies and both children are well. There is no history of recurrent miscarriages, stillbirth or neonatal stroke, or family history of bleeding diathesis or clotting disorders. Antenatal scans had revealed the fetus to be growing well until 30 weeks of gestation, when the weight dropped from the 40th to the 3rd percentile. At that time, the amniotic fluid volume, Doppler scan, and placental blood flow were normal. The mother had been asymptomatic, with normal blood cell count and erythrocyte sedimentation rate. Now at 33 weeks of gestation, the mother presents to the emergency department with reduced fetal movements over the previous week. She is admitted for observation. Antenatal ultrasonography confirms the earlier findings of intrauterine growth restriction and documented normal amniotic fluid volume and Doppler scan. She remains clinically well. However, cardiotocographic monitoring the next day reveals the presence of repeated decelerations suggestive of nonreassuring fetal status, prompting an urgent cesarean delivery. The infant is well at birth, and has a good cry. Apgar scores are 6 and 9 at 1 and 5 minutes, respectively. Birthweight is 1,160 g (<3rd percentile), length 39 cm (3rd-10th percentile) and head circumference 27.5 cm (3rd percentile). Soon after birth, the infant develops respiratory distress secondary to partially compensated metabolic acidosis (pH, 7.32; partial pressure of carbon dioxide, 19.5 mm Hg [2.6 kPa]; partial pressure of oxygen, 111 mm Hg [15 kPa]; base excess, −12; and bicarbonate, 14 mEq/L [14 mmol/L]). Clinical examination findings are unremarkable and vital signs are normal. No hypoglycemia or electrolyte abnormality is noted. Laboratory investigations on day 1 reveal thrombocytopenia (platelet count 39×103/μL [39×109/L]) and coagulopathy (prothrombin time 60 seconds, activated …

Skin Findings in a Patient with Sjogren's Syndrome.

Hypergammaglobulinemic purpura (HGP) is a syndrome constellating recurrent purpura, hypergammaglobulinemia, positive rheumatoid factor (RF), anti-Ro/La antibodies, and elevated erythrocyte sedimentation rate (ESR). We present a case of a 29-year-old female who was diagnosed with Sjogren's syndrome four years prior to presenting with rash on her lower extremities for a period of 6 months. Skin biopsy at the initial visit was consistent with leukocytoclastic vasculitis and was initiated on treatment for it. Her rash evolved into 2–5 mm scattered purpurae while she was on the treatment and a repeat biopsy showed extravasation of RBCs, a sparse mononuclear infiltrate with deposition of plasma cells, and no evidence of leukocytoclastic vasculitis, thus showing a transition from neutrophilic to mononuclear inflammatory vascular disease which is a rare occurrence. Hypergammaglobulinemic purpura sometimes turns out to be a challenging disease to manage and requires an integrated effort from the primary care doctors, rheumatologist, and dermatologist.

Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

A Case of Sjögren's Syndrome That Presented with Alcohol-induced Purpura

Sjögren syndrome (SS) is a systemic autoimmune disease that mainly affects the salivary and lacrimal glands. It may exist as a primary condition or in association with other systemic autoimmune diseases. Patients with SS usually complain of persistent dryness of the mouth and eyes and other features, including diverse general symptoms and cutaneous symptoms such as purpura. We report here on a case of 34-year-old woman who presented with purple non-blanching palpable purpura on both lower legs, and these lesions had developed soon after drinking alcohol 2 days previously. She had a 2 year history of repeatedly developing rashes in association with drinking alcohol. The physical examination showed dry eyes and dry mouth. The laboratory tests showed positivity for anti-Ro/SS-A antibody and RF and hyperimmunoglobulinemia. She was diagnosed as suffering with primary SS. Herein we report on a patient with primary SS and this patient initially presented with recurrent purpura in association with alcohol ingestion. Drinking alcohol had played a role as a possible aggravating factor for the cutaneous purpura of this patient with SS.

Henoch‐Schönlein purpura nephritis in children: risk factors, prevention and treatment

To identify risk factors for a child with Henoch-Schönlein purpura (HSP) either to develop nephritis (HSPN) or to contract progressive course and to obtain the currently available evidence on the efficacy of treatment options in both preventing and treating the established renal disease. Review of the literature published over the last two decades. Persistent or recurrent purpura, severe abdominal symptoms and an older age proved as the most significant risk factors for later HSPN. The risks of long-term renal impairment are the highest in children having at presentation nephritic/nephrotic syndrome and/or more than 50% of glomeruli occupied by large crescents or sclerosing lesions. Randomized controlled trials (RCT) do not support short course prednisone at presentation of HSP in preventing persistent renal disease. Many uncontrolled studies using various treatment regimens have reported outcomes considered better than expected. However, the data from RCTs are sparse and no treatment options for the established renal disease can be currently recommended based on RCTs. Severity and/or duration of extrarenal HSP symptoms and an older age are the most significant risk factors for developing HSPN, whereas clinical and histological severity at HSPN onset are in general predictive of a long-term renal impairment. The existing evidence does not support of short course prednisone in preventing persistent renal disease. A well-designed RCTs are needed in children with moderately severe or rapidly progressive (crescentic) HSPN.

Detection of serum allergen specific IgE in the child with recurrent auergic purpura

Objective To investigate the role of allergen specific IgE in the child with recurrent auergic purpura,and to detect the relation between all kinds of allergen and the disease.Methods The serum specific IgE of allergen detected by ELISA in 100 cases of the child with recurrent auergic purpura.Results 81 cases of serum allergen-specific IgE were over than 50ku/L(81%).52 cases(52%)were positive reaction to more than two kinds of allergens and 29 cases(29%)were positive reaction to one kind of allergen.Several familiar aeroallergen mixed molds (19/100),dermatophagoides(12/100)and mugwort pollens(9/100).The most familiar food fish(28/100).shrimpand crab(22/100),milk(18/100).protein(11/100).Conclusion It suggests that aeroallergens,fish,shrimp and crab play an important role in the pathogenesis of repeating child anaphy lactic purpura.Mixed molds and protein foods are important pathogens to the disease.To detect the serum specific IgE could help screen allergens,and have important role to prevent disease. Key words: Purpura; allergic; Immunoglobulin E; Allergens

Bleeding tendency in chronic neutrophilic leukemia

To define the clinical and pathologic features and natural history of chronic neutrophilic leukemia (CNL), as defined by the World Health Organization (WHO), Elliott critically reviewed the literature and identified a total of 34 patients meeting strictly defined WHO criteria for CNL [1]. Of the 34 patients, 9 died of intracranial hemorrhage and 3 demonstrated easy bruising. Elliot indicated that a disproportionate number of reports of intracranial hemorrhage must be considered in the context of an association with chemotherapy-induced thrombocytopenia during treatment of progressive disease. Furthermore, he described that excess hemorrhagic events were not a significant finding in chronic stable-phase disease in the absence of chemotherapy-induced thrombocytopenia. Here, we describe platelet dysfunction in a patient with CNL complicated by bleeding tendency. At the time this patient showed bleeding symptoms, she had not received chemotherapy and her platelet count was normal. On 20 August 2003, an 83-year-old Japanese woman was referred to our department for examination of bleeding tendency. She had a 3-year history of recurrent purpura and occasional nasal bleeding. Neither the patient nor any members of her family had a history of bleeding tendencies. On physical examination, purpura was detected on the face, back and extremities. A CT scan of the abdomen demonstrated splenomegaly. Peripheral blood showed: hemoglobin, 9.7 g/dl; platelets, 284 9 10/l; leukocytes, 29.0 9 10/l with 0.2% myelocytes, 0.6% metamyelocytes, 2.0% stabs, 90.8% segments, 1.0% eosinophils, 2.2% basophils, 1.2% monocytes and 2.0% lymphocytes. Neutrophil alkaline phosphatase (NAP) score was 352 (normal, 190–370). The serum concentration of granulocyte colonystimulating factor (G-CSF) was under 10.0 pg/ml. Immunoelectrophoresis did not show any M protein in serum or urine. The bone marrow was grossly hypercellular with marked myeloid hyperplasia and 1.0% blasts. There were no dysplastic features, minimal fibrosis, normal megakaryocytes and erythropoiesis. Chromosomal analysis demonstrated a normal karyotype. Reverse transcriptasepolymerase chain reaction (RT-PCR) studies failed to demonstrate the presence of BCR-ABL fusion. The patient was diagnosed as having CNL. Routine hemostatic tests demonstrated: bleeding time, more than 8 min (normal, 1–5 min); prothrombin time, 14.9 s (normal, 10.0–13.5 s); activated partial thromboplastin time, 39.8 s (normal, 25.0–40.0 s); plasma fibrinogen level, 295 mg/dl; plasma FDP concentration, 4.1 lg/ml (normal, below 10 lg/ml). Factor VIII activity was 180% (normal, 62–145%), von Willebrand factor antigen was 136% (normal, 50–150%), and ristocetin cofactor activity was 133% (normal, 50–150%). Activities of factor XIII and a2-plasmin inhibitor were 76% (normal, over 70%) and 86% (normal, 85–118%), respectively. Platelet aggregation induced by ADP, collagen, epinephrine or ristocetin was decreased when compared to that in the control. In contrast, arachidonic acid induced platelet aggregation was normal (Fig. 1). Similar patterns of abnormal platelet aggregation were repeatedly demonstrated on three different occasions. Flow cytometric analyses of her platelets for CD41 and CD42b expression showed normal patterns. These findings suggested that this patient had storage pool disease. In this disease, platelet aggregation induced by ADP, collagen, or epinephrine is impaired, but that induced by arachidonic T. Shigekiyo (&) J. Miyagi M. Chohraku K. Kawauchi E. Sekimoto A. Shirakami H. Shibata Department of Internal Medicine, Tokushima Prefectural Central Hospital, 1-10-3 Kuramoto-cho, Tokushima 770-0042, Japan e-mail: shigekiyo@tph.gr.jp

What may underlie recurrent purpura fulminans?

A woman presenting with recurrent purpura fulminans was eventually found to have inflammatory bowel disease. We suggest the inflammatory state resulted in a deficiency of functional protein C.

Efficacy of Tonsillectomy Plus Methylprednisolone Pulse Therapy for a Child with Henoch-Schoenlein Purpura Nephritis

Henoch-Schoenlein purpura (HSP) is a systemic disorder characterized by a leukocytoplastic vasculitis involving small vessels with the deposition of immunoglobulin A (IgA) immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. We report here an 11-year-old boy with Henoch-Schoenlein purpura nephritis (HSPN) accompanied by recurrent purpura and persistent nephropathy despite conventional therapy such as prednisolone, methylprednisolone pulse therapy and immunosuppressive agent (Mizoribine). The patient was treated with tonsillectomy plus methylprednisolone pulse therapy. This treatment decreased proteinuria, induced disappearance of microscopic hematuria, and improved renal pathological findings. Tonsillectomy plus methylprednisolone pulse is effective and useful therapy for some children with recurrent purpura and persistent nephropathy.

Juvenile‐onset hypergammaglobulinemic purpura and fetal congenital heart block

Waldenström's hypergammaglobulinemic purpura (HGP) is a rare chronic disorder characterized by recurrent purpura on the legs, a polyclonal increase in serum gamma-globulin, an elevated erythrocyte sedimentation rate and a positive rheumatoid factor. A 30-year-old primigravid woman with 14 years of HGP was found to have fetal bradycardia at 25 weeks' gestation. Laboratory investigations demonstrated positive anti-Ro/SSA and anti-La/SSB antibodies in the maternal serum. Cesarean delivery was performed at 39 weeks, and a 2750-g female infant was born with complete atrioventricular block. Fortunately, the neonatal period has been uneventful without need for pace-making. Maternal HGP exacerbated just after delivery, but resolved within 1 week without treatment. Physicians should be aware of the possible presence of neonatal lupus-related anti-Ro/SSA and anti-La/SSB autoantibodies in patients with HGP. Screening for these autoantibodies is important and could be used as a marker to identify and manage high-risk pregnancies.

Seltene Vaskulitiden als Hinweis auf Plasmozytom

We report on two female patients who presented with painful recurrent palpable purpura, ulcers and necroses on the extremities. The results of all examinations and laboratory tests considered together suggested a diagnosis of necrotizing leukocytoclastic vasculitis. Leukocytoclastic vasculitis is an inflammatory necrotizing condition of the superficial dermal vessels, presenting with variable clinical symptoms. In most cases it becomes manifest as palpable purpura, but hemorrhagic-necrotizing, bullous, nodular and urticarial presentations also occur. Common etiological factors include bacterial, viral or drug antigens, chronic infections (hepatitis B and C), non-Hodgkin lymphomas (monoclonal gammopathy, multiple myeloma), leukemia (hairy cell leukemia), and tumors (bronchial, breast, and gastric cancer) and also connective tissue disorders. In the course of the work-up, a plasmocytoma was discovered as the cause of the leukocytoclastic vasculitis, presenting in a similar way to livedo reticularis in one case and to pyoderma gangraenosum in the other.

Effects of Combined Antiviral Therapy on Asymptomatic Mixed Cryoglobulinemia in Naive Patients with Chronic Hepatitis C Virus Infection: A Preliminary Study

The clinical spectrum of mixed cryoglobulinemia embraces several manifestations: recurrent vascular purpura, weakness, arthralgia/arthritis, glomerulonephritis, peripheral neuropathies, and Raynaud's phenomenon. Mixed cryoglobulinemia is currently treated with steroids, low-antigen content diet, immunosuppressors, plasma exchange, and antiviral therapy, namely, alpha -interferon alone or, more recently, in association with ribavirin. In the present research, we verified the effectiveness of combined therapy with interferon and ribavirin on asymptomatic mixed cryoglobulinemia in naïve (never treated before) patients with chronic hepatitis C. We enrolled 50 consecutive patients, 31 males and 19 females, with chronic hepatitis C who showed a sustained response to combined antiviral therapy (interferon and ribavirin). Before treatment, cryoglobulins were detected in 25 subjects (50%). Only 1 of the 25 patients with asymptomatic mixed cryoglobulinemia had persistence of cryoglobulins at the end of the follow-up period. Unexpectedly, in 7 of 25 subjects without mixed cryoglobulinemia before treatment, cryoglobulins became detectable after antiviral therapy. Our present study first reports the onset of asymptomatic mixed cryoglobulinemia in hepatitis C virus patients after clearance of the virus from blood obtained with a combined antiviral treatment. Possible explanations are discussed. Our data also suggest that the appearance of a clinically evident mixed cryoglobulinemia cannot be excluded in this kind of subject.

Lack of association between anti-phospholipid antibodies (APLA) and Attention Deficit/Hyperactivity Disorder (ADHD) in children.

Numerous studies have shown the pathological influence anti-phospholipid antibodies (APLA) have on the physiology of the single neuron as well as the function of the entire human nervous system. The influence is well demonstrated in the antiphospholipid syndrome (APS). This syndrome is characterized by a triad of arterial or venous thrombotic events, recurrent fetal loss and thrombocytopenic purpura. The syndrome exhibits different neurological pathologies such as: chorea, seizures, transverse myelopathy, migraine, cerebral ataxia, hemiballismus and transient global amnesia, which are not fully explained by the procoagulopathic trait of APLA. A study on mice induced with APS demonstrated hyperactive behavior when compared to the control group. The information gathered from these different studies raised the question whether APLA has any part in the etiology of Attention Deficit/Hyperactive Disorder (ADHD) in children. We compared 41 children diagnosed with ADHD to a control of 28 healthy children. Blood drawn from the two groups was screened using ELISA for the presence of anti-cardiolipin antibodies, antiβ2GP antibodies, anti-phosphatidyleserine antibodies and anti-ethanolamine antibodies. The results show no significant difference in the level of antiphospholipid antibodies (APLA) measured between the children diagnosed with ADHD and the control group.