Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase.

BACKGROUND: Acute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK). CASE PRESENTATION: A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus. CONCLUSION: In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

Mutaciones privadas en el gen de la miofosforilasa: primer caso en un paciente de origen latinoamericano / Private mutations in the myophosphorylase gene: The first case in a patient of latin american descent

La enfermedad de McArdle (glicogenosis tipo V) es una miopatía metabólica común causada por unadeficiencia de la actividad de la miofosforilasa. La enfermedad se debe a mutaciones en el gen de la miofosforilasa (PYGM) y está presente en un gran número de países. Caso clínico. Varón de 13 años de edad que sufrió un episodio de dolor muscular y presentó unos niveles elevados de creatincinasa en plasma, mioglobinuria y debilidad de la musculatura proximal moderada, después de un corto pero vigoroso ejercicio. El paciente nació en Ecuador y fue adoptado por una familia española.Se analizó completamente el gen de la miofosforilasa y se encontró que el paciente era portador de una mutación consistente en pérdida de sentido, un cambio homocigótico de una G por una A en el exón 11, cambiando una valina por una metionina en el codón 456 (V456M). La mutación previamente descrita afecta a un aminoácido conservado en la enzima y no estaba presenteen la población control estudiada. Conclusiones. Estos hallazgos demuestran la presencia de la enfermedad de McArdle en varios grupos étnicos y sugiere que el origen étnico del paciente es importante para decidir qué mutaciones deberían analizarse primero en los estudios diagnósticos moleculares (AU)

McArdle's disease (glycogenoses type V) is a common metabolic myopathy caused by deficientmyophosphorylase activity. The disease is due to mutations in the myophosphorylase (PYGM) gene and is present in a large number of countries. Case report. A 13-year-old male who suffered an episode of muscle pain and offered increased levels of creatinkinase in plasma, myoglobinuria and mild weakness of the proximal muscles, after short but vigorous exercise. The patient was born in Ecuador and was adopted by a Spanish family. The myophosphorylase gene was analysed completely andthe patient was found to be a carrier of a missense mutation, a homozygous change where a G is replaced by an A in exon 11, changing a valine for a methionine in codon 456 (V456M). The mutation described above affects an amino acid that is conserved in the enzyme and which was not present in the control population that was studied. Conclusions. These findings show thepresence of McArdle’s disease in several ethnic groups and confirm that the ethnic origin of the patient is important when it comes to deciding what mutations should be analysed first in molecular diagnosis studies (AU)

Muscle cell injury, haemolysis and dark urine in children with falciparum malaria in Papua New Guinea.

During a prospective study of red cell variants and severe malaria in children, a surprising observation was the occurrence of dark urine. Children were grouped according to urine findings: 22 had dark urine that contained a haem protein (Group I), 93 had urine of normal colour that contained a haem protein (Group II) and 236 had normal urine (Group III). To investigate the cause of dark urine, haemolysis and muscle cell injury were assessed. Intravascular haemolysis was greater in Group I than in Groups II and III. However, anaemia was more severe in Group III and is likely to have resulted mainly from extravascular haemolysis. Median plasma myoglobin concentrations were greater in Groups I and II than Group III (P = 0.00060). Plasma myoglobin was greater in children with cerebral malaria, hyperlactataemia and those who died but was not associated with acidosis. Urine myoglobin was greater in Group I than Groups II and III (P = 0.00054). It is likely that both haemoglobin and myoglobin contributed to dark urine. The association between muscle cell injury and coma suggests sequestration of parasitized red cells as a common underlying pathology. In malaria, hyperlactataemia may result directly from breakdown of muscle protein as well as tissue hypoxia.

The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis.

OBJECTIVE: Cardiac troponin I (cTnI) is considered the most specific marker of cardiac muscle injury. We encountered several patients with rhabdomyolysis and elevated cTnI, although they did not otherwise have evidence of cardiac injury. We determined the prevalence of false-positive cTnI in emergency department (ED) patients with rhabdomyolysis. METHODS: We conducted a retrospective cohort study of ED patients admitted with a diagnosis of rhabdomyolysis. Patients were included in the study if they had a serum creatine kinase (CK) of 1000 U/L or greater and at least one serum cTnI determination. Patients with positive cTnI were considered true positives if they had either electrocardiography (EKG) or echocardiography abnormalities; false positives if both the EKG and the echocardiography were considered normal; or indeterminate if they did not have both an EKG and an echocardiogram. The primary outcome of the study was the prevalence of false-positive cTnI. Secondary outcomes included risk stratification by cocaine use, myoglobinuria, and renal failure and correlation of peak CK and troponin levels. RESULTS: One hundred nine patients were included in the final analysis; 55 (50%) patients had a positive cTnI. Of the 55 patients with positive cTnI, 32 (58%) were true positives, 18 (33%) were false positives, and 5 (9%) were indeterminate. The prevalence of false-positive cTnI was 17% (18/109, 95% confidence interval 0.10-0.25). There was no association between false-positive cTnI and cocaine use, renal failure, or myoglobinuria. There was poor correlation between peak CK and peak cTnI levels (r = -.08, 95% confidence interval -0.34 to 0.19). CONCLUSION: The prevalence of false-positive cTnI in ED patients with rhabdomyolysis is 17%.

Post-mortem urinary myoglobin levels with reference to the causes of death.

To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48h. A high (>1000 ng/ml), moderate (100-1000 ng/ml), slight (50-100 ng/ml) and not significant (<50 ng/ml) elevation of urinary myoglobin were observed in 26, 43, 31 and 110 cases, respectively. Half the highly elevated cases were those with a survival time over 24h. In cases of minor muscle injury such as head trauma, elevation of urinary myoglobin level was closely related to longer survival. In acute/subacute deaths with a post-mortem interval within 48h, a significant difference was observed in relation to the blood carboxyhemoglobin (COHb) levels of fire victims: myoglobinuria over 100 ng/ml was more frequently and markedly observed in cases with COHb below 60% than over 60%, suggesting muscle damage in fatal burns. Similar elevation was observed in heat stroke victims, and also in some cases of acute and subacute death from polytrauma, asphyxiation, drowning, electricity and spontaneous cerebral bleeding, but not in myocardial infarction. Thus, it was suggested that high post-mortem urinary myoglobin levels in acute and subacute death cases may be a possible indicator of antemortem massive skeletal muscle damage as well as exertional muscle hyperactivity or convulsive disorders associated with hypoxia.

Rhabdomyolysis in autosomal dominant progressive external ophthalmoplegia.

Multiple mtDNA deletions have been reported to be a cause of inherited recurrent myoglobinuria. We report a 57-year-old man with autosomal dominant progressive external ophthalmoplegia and multiple mtDNA deletions who developed acute rhabdomyolysis provoked by alcohol. A repeated alcohol intake resulted in a 57-fold increase in serum myoglobin. Patients with mitochondrial myopathy and multiple mtDNA deletions, regardless of associated phenotype and mode of inheritance, may develop rhabdomyolysis.

[Assessment of regional and systemic toxicity of isolated hyperthermic extremity perfusion with tumor necrosis factor-alpha and melphalan]. / Erfassung regionaler und systemischer Toxizität der isolierten, hyperthermen Extremitätenperfusion mit Tumor-Nekrose-Faktor alpha und Melphalan.

Following isolated limb perfusion (ILP) with TNF alpha and melphalan the damage to muscle tissue and its systemic consequences in terms of myoglobinemia and myoglobinuria as well as the activation of the cytokine cascade were investigated. We measured the compartmental pressure of the limb during and after perfusion and determined the serum changes of myoglobin, creatine kinase (CK), interleukin (IL)-6, IL-1, s-IL-2-receptor, TNF-receptor, and ICAM-1 levels. The compartmental pressure rose significantly during ILP and decreased after reperfusion. Following its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times normal values and the increase occurred significantly earlier than that of CK, thus enabling judgement of the risk of renal failure (crush kidney syndrome). The elevation of serum IL-1 and IL-6 values correlated with the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated counter-maneuvers. Our data, although obtained from ILP with TNF alpha, could be used to monitor toxicity also when other drug regimens are administered.

Fatal poisoning by MDMA (ecstasy) and MDEA: a case report.

The first observation of lethal recreational use of MDMA (ecstasy) and MDEA in Italy is reported, together with extensive toxicological and histopathological documentation. Findings such as disseminated intravascular coagulation, rarely reported before, are colocated in the framework of the toxic syndrome for a better definition of criteria for forensic diagnosis.

Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer.

A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombotic thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure.

Physiologic amputation prevents myoglobinuria from lower extremity myonecrosis.

Myoglobinuria secondary to myonecrosis is a proven cause of renal failure, especially in critically ill patients. Physiologic amputation or cryoamputation has been used at our institution for the past two decades as a safe and effective treatment for lower extremity infection, intractable rest pain, and irreversible myonecrosis. We retrospectively studied five critically ill patients with myonecrosis of lower extremities associated with myoglobinuria. The etiology of myonecrosis included preexisting peripheral vascular disease or crush injury to the lower extremities. It was determined that all five patients were too ill to undergo emergency amputation. Myoglobinuria was documented in all five patients and cleared within 24 hours of physiologic amputation in four patients. All five patients had elevated creatine phosphokinase levels (mean 20,270 mU/mL, range 12,090 to 43,164 mU/mL) that significantly decreased within 48 hours of physiologic amputation (mean 6,488 mU/mL, range 2,250 to 13,580 mU/mL). Mechanical ventilation and cardiovascular support were required in four patients. All patients had transient episodes of renal insufficiency with two progressing to anuric renal failure and requiring dialysis. One patient's renal failure resolved after 56 days, but the other patient died of a cerebrovascular accident 22 days after initiation of physiologic amputation. The mean duration of physiologic amputation was 15.6 days (range 5 to 32 days) with no significant complication due to physiologic amputation. All five patients had surgical amputation successfully. Three patients survived. The two deaths in the study were due to a cerebrovascular accident in one patient and a cardiopulmonary arrest in another. Physiologic amputation is a treatment option that halts myonecrosis, prevents myoglobinuria, and lessens the risk of associated acute renal failure. Physiologic amputation may be appropriately used in patients with myoglobinuria due to extremity myonecrosis who are deemed too critically ill to survive emergency amputation.

Rhabdomyolysis following total hip arthroplasty.

We report six cases of contralateral limb involvement during total hip arthroplasty including swelling of the gluteal muscle compartments, rhabdomyolysis, myoglobinuria, and sciatic nerve palsy. The risk factors for such complications include obesity, prolonged operative time, and positioning in the lateral decubitus position. The laboratory and clinical findings are consistent with a gluteal muscle crush-injury with consequent compartment syndrome. The patients should be treated conservatively as symptoms can be expected to resolve.

Atypical myoglobinuria: an acute myopathy in grazing horses.

Four out of 12 horses grazing a field in Berkshire, England, suffered a prostrating illness and died within 12 to 72 h. Serum biochemical abnormalities, including markedly elevated muscle enzymes, were demonstrated and at post mortem widespread myodegeneration was found in both skeletal muscle and myocardium. Urine analysis revealed myoglobinuria, and renal changes were seen histologically. Although similar pathologically, the clinical syndrome and circumstances of the outbreak were not typical of equine exertional rhabdomyolysis (EER). The outbreak bore a striking resemblance to other reported sporadic outbreaks of an atypical myoglobinuria occurring in grazing horses. A number of potential aetiological and contributory factors (including herbicide toxicity) were considered, but the aetiology remains unresolved.

Myoglobinuria in chronic renal failure.

Serum and urine myoglobin levels were determined on 14 patients with stable chronic renal failure. Serum myoglobin ranged from 38 to 350 ng/mL. Eleven patients had myoglobinuria between 15 and 250 ng/mL; none developed myoglobinuric renal failure. Fractional excretion of myoglobin in the myoglobinuric patients increased as creatinine clearance decreased, although there was no correlation between filtered load and excretion rate of myoglobin. This confirms that renal failure leads to hypermyoglobinemia and usually to myoglobinuria. Surviving nephrons tend to reabsorb less of the filtered load of myoglobin as renal function diminishes.

[Myoglobinuria in malabsorption after small bowel resection]. / Myoglobinurie bei Malabsorption nach Dünndarm- resektion.

A patient with subtotal small bowel resection after mesenterial vein thrombosis presented with muscular weakness and pain. An increase in the activities of enzymes of muscular origin and of myoglobin in serum was found and myoglobinuria was detected. Muscle damage in this patient is attributed to electrolyte disturbances following extensive small bowel resection.