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.

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.

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.

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.

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.

Mancha negra en el talón / Black heel

El «talón negro» o black heel es una lesión benigna, frecuente en adolescentes que practican deporte con asiduidad, producida por el roce repetido con el calzado, que se manifiesta como una mancha marrón negruzca en zona del talón. Se resuelve sola (sobre todo si cesa el ejercicio) sin necesidad de tratamiento. Es importante conocer esta entidad para diferenciarla del melanoma maligno, y así evitar derivaciones innecesarias a Servicios de Dermatología. Las consultas virtuales enviando fotos a los especialistas podrían ayudar en casos dudosos. Presentamos dos casos de talón negro en dos jóvenes deportistas (AU)

The black heel is a benign lesion, common in teenagers that often play sport, produced because of the continuous contact with the sport shoe, that manifests like a brown-black spot located at the touch zones of the heel. It disappears without any treatment, especially if the sport stops. It is important to know this entity to differentiate it from malignant melanoma, and avoid unnecessary derivations to dermatologists. Virtual consultations sending photos to specialists could help in doubtful cases. We present two cases of black heel in two young athletic children (AU)

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.

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.

Mitochondrial diseases caused by toxic compound accumulation: from etiopathology to therapeutic approaches.

Mitochondrial disorders are a group of highly invalidating human conditions for which effective treatment is currently unavailable and characterized by faulty energy supply due to defective oxidative phosphorylation (OXPHOS). Given the complexity of mitochondrial genetics and biochemistry, mitochondrial inherited diseases may present with a vast range of symptoms, organ involvement, severity, age of onset, and outcome. Despite the wide spectrum of clinical signs and biochemical underpinnings of this group of dis-orders, some common traits can be identified, based on both pathogenic mechanisms and potential therapeutic approaches. Here, we will review two peculiar mitochondrial disorders, ethylmalonic encephalopathy (EE) and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), caused by mutations in the ETHE1 and TYMP nuclear genes, respectively. ETHE1 encodes for a mitochondrial enzyme involved in sulfide detoxification and TYMP for a cytosolic enzyme involved in the thymidine/deoxyuridine catabolic pathway. We will discuss these two clinical entities as a paradigm of mitochondrial diseases caused by the accumulation of compounds normally present in traces, which exerts a toxic and inhibitory effect on the OXPHOS system.

[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.