Introduction

The current H1N1 influenza A virus pandemic is allowing us to identify different aspects regarding the clinical features of this entity. Symptoms published are closely related with the seasonal influenza [10]. During these annual epidemics, it is frequent to observe children with sudden onset of calf pain and refusal or difficulty to walk. After the first description of benign acute myositis (BAM) in 1957 [7], this process has been associated with influenza B virus infection and occasionally with other viruses (influenza A, parainfluenza, adenovirus, and herpes simplex) [1, 8, 9]. Recently, a case of BAM has been related with H1N1 influenza A virus infection [6]. Here, we report the clinical presentation and laboratory studies of 4 children with BAM associated with a proven H1N1 influenza A virus infection in our emergency department.

Case reports

The characteristics of our children are shown in Table 1. The mean age of the four patients (2 boys and 2 girls) was 7 years old (range, 2–11 years). The main complaint was a bilateral calf pain and difficulty to walk from 10 to 36 h before their admittance. All of them referred previous history of moderate fever, and three showed classical flu symptoms. Clinical examination showed rhinorrhea, cough, and pharyngitis, but the main clinical signs were located in their calves, which were tender on palpation and on stretching. We did not observe any specific antalgic gait. No inflammatory signs were observed, and neurological examination of the legs was normal.

Table 1 Clinical and laboratory values of the patients

Laboratory values showed a normal leukocyte count, with lymphocyte prevalence in three patients, no band forms were observed. Platelet count was between normal ranges. Inflammatory parameters like C-reactive protein were normal, with a mean value of 0.47 mg/dl (normal, <0.8 mg/dl). Serum muscular enzymes were increased with values of creatine phosphokinase (CPK) of 1549 U/l (normal, <195) and aspartate aminotransferase (AST) of 72 U/l (normal, <56). Urine samples were checked by dipstick without abnormalities. An acute and convalescent paired serology showed no evidence of recent adenovirus, respiratory syncitial virus, mycoplasma, cytomegalovirus, herpes virus, or Epstein-Barr virus infections. Novel H1N1 influenza A virus was identified on a nasopharyngeal swab by immunochromatography (IC) in three patients and by specific polymerase chain reaction (PCR) in all of them.

All patients were managed on an out-patient basis under close surveillance, and oseltamivir was not given to any of them. They were seen in our hospital 2 and 4 weeks later. During this period, they totally recovered in a mean time of 4 days (range, 2–7 days) with normalization of CPK and AST serum values at the second week control. At discharge, physical exam and gait were normal.

Discussion

The first report of “Myalgia Cruris Epidémica” by Lundberg [7] described a clinical entity that affects children, especially boys, with a sudden onset of calf pain that causes difficulty to walk and increased levels of serum CK. It had rarely been seen in adults and was followed by a rapid and total recovery in the next few weeks. Later on, it was clearly associated with influenza B infection [9], although in a report covering five patients, similar incidence of BAM has been found in cases associated with influenza B, as well as influenza A virus [1]. During the recent outbreak of a novel variant of influenza A virus (H1N1) we have observed four episodes of BAM. All of them showed the classical symptoms of painful muscle tenderness specifically localized at the gastrocnemius–soleus muscles and were unable to walk by themselves. The gait was abnormal for all patients, but we could not find any of the typical gaits described [8]. Despite the small number of patients, no male predominance was observed. Laboratory values matched those of previous reports, showing a transient increase of CPK serum levels. Although the presence of rhabdomyolysis has been reported in severe cases [3], we have not observed it, and checking myoglobinuria in urine samples of each patient by dipstick was ruled out. However, given the small number of patients observed, we cannot underestimate the potential risk of rhabdomyolysis in H1N1 influenza A virus infection, since its incidence is higher in seasonal influenza A virus infection [1, 3, 8]. We have not performed other studies as electromyography or biopsies in our patients given the typical BAM symptoms at the onset, the good evolution observed in our patients, and the unspecific findings reported for these studies in similar cases [8]. In our patients, clinical and biochemical controls after the onset revealed a benign course that has allowed managing them safely as outpatients with a total recovery and without recurrences observed.

Nowadays, the pathogenesis of BAM remains unclear, but because the H1N1 variant belongs to the influenza virus group [10], it could be hypothesized that they both could share the same pathways to produce myositis. Due to the absence of muscle deposits of immunoglobulin and complement, it has been suggested that myositis may be due to direct muscle viral infection [11]. This hypothesis has been reinforced by the descriptions of myxovirus-like particles that have been observed by electron microscopy in a muscle biopsy from a patient with BAM [5] and in another muscle biopsy of a patient that was positive for influenza B [4]. Difficulty to recover virus from affected muscles could be related with a non-permissive infection that does not produce progeny virions [2]. However, given their prevalence in children, it could simply reflect an age-related response to a viral infection that could be explained by the increased tropism towards immature muscle cells, which has been reported for influenza virus in experimental studies with animals [12]. Furthermore, the possibility that own virus would act as a trigger in children genetically predisposed or with an as-yet unknown underlying metabolic defect [8] has also been emphasized.

As it has been demonstrated, influenza viruses, variant H1N1 as well, can produce a variety of muscle disorders, especially BAM. That is why, in the current H1N1 influenza virus pandemic, the BAM diagnosis must be suspected in those children with flu symptoms and difficulty to walk, taking this into account might help avoiding unnecessary studies and therapies. Further viral studies in future cases may be necessary for a better understanding of the real pathogenesis related to this syndrome.