Retiform purpura: Workup and therapeutic considerations in select conditions.

In this article we focus on updates in select etiologies of retiform purpura. These causes of retiform purpura, in addition to bacterial or fungal sepsis, disseminated intravascular coagulation, purpura fulminans, and catastrophic antiphospholipid syndrome, are important diagnoses with potential for morbidity and mortality. Important aspects in the pathophysiology, patient demographics and risk factors, updates in the diagnostic workup, histopathology, and treatment of these specific conditions are discussed.

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection.

BACKGROUND: Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. METHODS: This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. RESULTS: Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. CONCLUSIONS: The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients' renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

Laser acupuncture improves skin color deformation by cupping: A pilot study.

Negative pressure of cupping induces skin deformation such as ecchymosis and purpura in a circular shape. Thus, there is a desire to treat skin before depigmentation and scarring occurs. Therefore, we introduce laser therapy, a widely used technique treat pigmentation in dermatology. Various parameters of laser therapy can be applied, so to determine the optimal exposure parameters that do not damage the surrounding tissues, the subjects were divided into four groups: a non-stimulation group and three laser groups (4 J/cm2 group, 6 J/cm2 group, and 8 J/cm2 group). We selected the wavelength and output of laser as follows: 660nm and 50mW. The 40 were divided into four groups of 10. In the first experiment, we measured skin temperature using Digital infrared thermography in order to observe whether the laser could cause heat damage. In the second experiment, each group received the assigned laser therapy protocol every 24 hours for 72 hours. We obtained a skin image using a cross polarization technique. Previous studies have shown that a*and E.I (erythema index) represent the degree of skin erythema (hemoglobin content). M.I (melanin index) indicates the degree of skin pigmentation (melanin content). Hence, skin color information was analyzed with the a*, erythema index (E.I), and melanin index (M.I) for 72 hours. None of the laser exposure parameters led to skin damage by heating or energy dissipation. The results of a*, E.I, and M.I of all groups showed the different recovery rates towards the normal skin color information before cupping. As energy density increases, the result of a* and E.I showed the fast recovery rate. There was no significant different between M.I at non-stimulation group and M.I at 4 J/cm². Therefore, the least energy density as 6 J/cm² is need for the recovery of melanin content. The a*, E.I, and M.I at 8 J/cm² group rather than other groups were significantly recovered to normal skin color. In conclusion, the laser therapy (energy density: 8 J/cm²) has a significant recovery of the skin erythema and skin pigmentation except to skin damage.

Granulomatous pigmented purpuric dermatosis: report of a case with atypical clinical presentation including dermoscopic findings.

Granulomatous pigmented purpuric dermatosis (PPD) is a rare and poorly recognized histological variant of PPD, which commonly affects the distal extremities of mainly Far East Asian patients. Many of the reported cases are associated with hyperlipidemia or other associated systemic derangements. The authors hereby describe an additional case of granulomatous PPD affecting a 56-year-old Caucasian woman presenting unusually as a solitary lesion confined to the lower back. The report also describes dermoscopic findings, summarizes clinicopathological features of all the cases published till date, and discusses the histopathological differential diagnosis.

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.

[Capillary fragility and some hemostatic parameters in patients with rosacea].

The aim of the study was to investigate the association between capillary fragility and some hemostatic parameters, lipid profile in patients with rosacea. 50 patients (30 women and 20 men) aged 35 to 65 years were under observation. Control group consisted of 50 healthy persons, adequate to comparison group by sex and age. To determine the resistance of the capillary, Rumpel-Leede cuff (tourniquet test) was used which consists in determining the formation of petechial hemorrhages on the skin in the area of ​​short-term increase in venous pressure. The hemostatic system was evaluated in terms of prothrombin and thrombin time. Content of fibrinogen and fibrinolytic activity of blood were determined also. The serum lipid profile was studied by means of the following parameters: total cholesterol, triglycerides, HDL (high density lipoprotein), LDL (low density lipoproteins). The survey revealed that in 25 patients the arm cuff test was positive, whereas in the control group, only 2 cases it was weakly positive. Manifestations of hypercoagulation were found in half of patients with a positive cuff test, almost in half of the patients an increased level of fibrinogen and the reduced fibrinolytic activity in blood serum has been revealed. Significant correlation with lipid metabolism have not been identified. Phenomenon of hypercoagulation in rosacea patients on the one hand suggests the existence of processes of microcoagulation, on the other hand the connection with the results of a cuff test can be used to predict the severity of the dermatosis and the possible risk for developing of cardiovascular disease.

Flat spin and negative Gz in high-altitude free fall: pathophysiology, prevention, and treatment.

INTRODUCTION: Red Bull Stratos was a commercial program that brought a test parachutist protected by a full pressure suit to 127,852 ft (38,964 m), via a stratospheric balloon with a pressurized capsule, from which he free fell and subsequently parachuted to the ground. In light of the uniqueness of the operation and the medical threats faced, medical protocols specific to distinctive injury patterns were developed. One unique threat was that of a flat spin during free fall with resultant exposure to -Gz (toe-to-head) acceleration. In preparation for stratospheric free fall, the medical team conducted a review of the literature on the spectrum of human and animal injury patterns attributable to -Gz exposures. Based on the findings, an emergency medical field response protocol was developed for the rapid assessment, diagnosis, and treatment of individuals suspected of -Gz injury. METHODS: A systematic review was conducted on available literature on human and animal studies involving significant -Gz exposure, with subsequent development of an applicable field treatment protocol. RESULTS: The literature review identified pathophysiologic processes and mitigation strategies that were used to develop a prevention and treatment protocol, outlining appropriate interventions using current best medical practices. A medical field treatment protocol was successfully established for the high-altitude balloon program. DISCUSSION: Available literature provided insight into best medical practices for the prevention and treatment of significant -Gz exposures during high-altitude parachute activity. Using the protocol developed for the field medical response, injuries from sustained -Gz exposure can be effectively managed in similar high-altitude and space operations.

[Exercise induced vasculitis].

Exercise induced vasculitis (or purpura) is usually misdiagnosed and ignored in the literature, although it is not uncommon. We report two female patients who developed a rash on the lower legs after walking all day long. The rash was red, itchy with a burning sensation. The lesions resolved after a few days with and without steroid treatment. Allergic etiology was suspected, therefore they were sent to the allergy clinic for evaluation. Exercise-induced vasculitis tends to occur in healthy people, especially in hot weather. Extensive investigation with blood or allergy tests is not needed.

Disruption of mitochondrial homeostasis in organic acidurias: insights from human and animal studies.

Organic acidurias or organic acidemias constitute a group of inherited disorders caused by deficient activity of specific enzymes of amino acids, carbohydrates or lipids catabolism, leading to large accumulation and excretion of one or more carboxylic (organic) acids. Affected patients usually present neurologic symptoms and abnormalities, sometimes accompanied by cardiac and skeletal muscle alterations, whose pathogenesis is poorly known. However, in recent years growing evidence has emerged indicating that mitochondrial dysfunction is directly or indirectly involved in the pathology of various organic acidemias. Mitochondrial impairment in some of these diseases are generally due to mutations in nuclear genes of the tricarboxylic acid cycle or oxidative phosphorylation, while in others it seems to result from toxic influences of the endogenous organic acids to the mitochondrion. In this minireview, we will briefly summarize the present knowledge obtained from human and animal studies showing that disruption of mitochondrial homeostasis may represent a relevant pathomechanism of tissue damage in selective organic acidemias. The discussion will focus on mitochondrial alterations found in patients affected by organic acidemias and by the deleterious effects of the accumulating organic acids on mitochondrial pathways that are crucial for ATP formation and transfer. The elucidation of the mechanisms of toxicity of these acidic compounds offers new perspectives for potential novel adjuvant therapeutic strategies in selected disorders of this group.

Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome.

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. To study the molecular effects of ETHE1 p. D165H mutation, we employed mass spectrometry-based mitochondrial proteome and phosphoproteome profiling in the human skeletal muscle. Eighty-six differentially altered proteins were identified, of which thirty-seven mitochondrial proteins were differentially expressed, and most of the proteins (37%) were down-regulated in the OXPHOS complex-IV. Also, nine phosphopeptides that correspond to eight mitochondrial proteins were significantly affected in EE patient. These altered proteins recognized are involved in several pathways and molecular functions, predominantly in oxidoreductase activity. This is the first study that has integrated proteome and phosphoproteome of skeletal muscle and identified multiple proteins associated in the pathogenesis of EE.

Cutaneous Manifestations of COVID-19.

Patients with coronavirus disease 2019 (COVID-19) present with multisystem signs and symptoms, including dermatologic manifestations. The recent literature has revealed that dermatologic manifestations of COVID-19 often are early onset and provide helpful cues to a timely diagnosis. We compiled the relevant emerging literature regarding the dermatologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so that physicians can be aware of the various clinical cutaneous presentations in this time of high incidence of COVID-19.

Infective Endocarditis-Associated Purpura and Glomerulonephritis Mimicking IgA Vasculitis: A Diagnostic Pitfall.

BACKGROUND: Purpura and glomerulonephritis are typical presentations in IgA vasculitis. Infective endocarditis mimicking IgA vasculitis by presenting with glomerulonephritis and purpura is rarely reported. METHODS: We searched for cases with infective endocarditis-associated purpura and glomerulonephritis in a tertiary hospital in China and retrospectively reviewed their clinicopathological features. Differential diagnosis and treatment in patients with infective endocarditis-associated purpura and glomerulonephritis were discussed. RESULTS: A total of 20 cases with infective endocarditis-associated purpura and glomerulonephritis were identified among 548 cases with infective endocarditis in our center during an 8-year period: 7 of the 20 cases (35%) were initially misdiagnosed as IgA vasculitis and 10 cases (50%) presented with left-sided endocarditis caused by Streptococcus viridans. Fever (100%, 20 out of 20), prior valvular deformities (80%, 16 out of 20), cardiac murmur (95%, 19 out of 20), splenomegaly (84%, 16 out of 19), embolism (55%, 11 out of 20), and hypocomplementemia (76%, 13 out of 17) were present in most patients. Crescents and mesangial hypercellularity with or without endothelial hypercellularity were the primary findings on light microscopy, with C3-dominant deposition on immunofluorescence. But IgA-dominant staining was also observed (40%, 2 out of 5). In patients with rapidly progressive glomerulonephritis, patients with complete recovery of renal function had shorter disease duration and higher ratio (67% vs 20%) of immunosuppressive therapy compared with patients with partial recovery. CONCLUSIONS: Infective endocarditis-associated glomerulonephritis and purpura can closely mimic IgA vasculitis. Differential diagnosis is challenging, particularly when typical presentations of infective endocarditis are absent. In adults with presentations like IgA vasculitis, infective endocarditis should be evaluated through comprehensive clinical and pathological investigations. Immunosuppressive therapy can be considered in patients with severe glomerulonephritis who do not improve after proper anti-infective therapy.

Acute Strokelike Presentation and Long-term Evolution of Diffusion Restriction Pattern in Ethylmalonic Encephalopathy.

Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the ETHE1 gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.

[Post transfusion purpura--a serious underdiagnosed delayed post-transfusion event]. / Skaza krwotoczna maloplytkowa--rzadko rozpoznawane pózne powiklanie poprzetoczeniowe.

UNLABELLED: Post-transfusion purpura (PTP), a delayed post-transfusion event, is underdiagnosed, not only in Poland. Thrombocytopenia results from the destruction of patients' and transfused platelets by platelet specific antibodies (anti-HPA). The incidence of PTP is not estabilished. THE AIM: Analysis of 10 cases with PTP diagnosed in Poland during last 25 years. MATERIAL AND METHODS: 9 women and 1 man with normal platelet count who developed thrombocytopenia with diathesis haemorrhagica after transfusion of red cells or/and platelets. Platelet specific antibodies (anti-HPA) were examined by the platelet immunofluorescence test and by the monoclonal immobilization of platelet antibodies (MAIPA) assay; leucocyte antibodies by standard lymophocytotoxicity test (LCT). RESULTS: In all 10 patients the PTP was diagnosed because: 1) thrombocytopenia with diathesis haemorrhagia occured 3-10 days after the transfusion (in 5 cases blood was transfused during the operation), 2) in all the patients anti-HPA were detected (in 9- anti-HPA-1a, in 1 case anti-HPA-3a), 3) a primary HPA alloimmunization was very probable. A recovery of platelets count occured in 6 patients within 8-34 days after corticosteroids and/or IVIG, however, therapeutic effect of them was difficult to assess due to a great probability of spontaneous remission up to 1 month. Four patients died due to their basic disease although the impact of the PTP cannot be excluded. CONCLUSION: The diagnosis of PTP was possible because of the detection of anti-HPA antibodies in patients who developed thrombocytopoenia after blood transfusion.