Mycobacterium marinum: a rare cause of chronic lymphocutaneous syndrome.

We investigated the prevalence of Mycobacterium marinum lymphadenitis and describe 4 children with the disease. The database of the microbiology laboratory of a tertiary pediatric medical center was searched for all cases of nontuberculous mycobacterial lymphadenitis from 1996 to 2016. M. marinum lymphadenitis was defined as isolation of the pathogen from a lymph node or from a skin lesion with an enlarged regional lymph node. M. marinum was isolated from lymph nodes in 2 of 167 patients with nontuberculous mycobacterial lymphadenitis and from skin lesions in 2 children with skin lesions and regional reactive lymphadenitis, yielding a 2.4% prevalence of M. marinum lymphadenitis. All 4 affected children were younger than 7 years and had been referred for evaluation of enlarged lymph nodes. Preauricular/submandibular and inguinal lymph nodes (n = 2 each) were involved. Three patients had skin traumas and visited the same natural spring. The diagnosis was delayed because a history of aquatic exposure was initially missed. Two children were managed with anti-mycobacterial antibiotics and 2 by observation only. All showed good resolution. CONCLUSION: A detailed history, specifically regarding exposure to spring water sources, in cases of lymphocutaneous syndrome can point to the diagnosis of M. marinum infection. What is Known: • M. marinum can cause chronic nodular or ulcerative skin infections. • Lymphadenitis due to M. marinum has rarely been reported. What is New: • M. marinum infection can present as isolated chronic lymphadenitis; it accounts for about 2.4% of all cases of nontuberculous mycobacterial lymphadenitis and it tends to occur in noncervicofacial regions relative to infections of other nontuberculous mycobacterial species. • Careful history taking including water source exposure, especially in association with skin trauma, can point to the correct diagnosis in children with chronic lymphadenitis.

Vomiting and migraine-related clinical parameters in pediatric migraine.

OBJECTIVE/BACKGROUND: To investigate the characteristics of vomiting in pediatric migraineurs and the relationship of vomiting with other migraine-related parameters. METHODS: The cohort included children and adolescents with migraine attending a headache clinic of a tertiary pediatric medical center from 2010 to 2016. Patients were identified by a retrospective database search. Data were collected from medical files. The presence of vomiting was associated with background and headache-related parameters. RESULTS: The study group included 453 patients, 210 boys (46.4%) and 243 girls (53.6%), of mean age 11.3 ± 3.7 years. Vomiting was reported by 161 patients (35.5%). On comparison of patients with and without vomiting, vomiting was found to be significantly associated with male gender (54% vs 42.1%, P < .018), younger age at migraine onset (8.0 ± 3. years vs 9.6 ± 3.7 years, P < .001), younger age at clinic admission (10.5 ± 3. years vs 11.6 ± 3.6 years, P = .002), higher rate of awakening headache (64.1% vs 38.7%, P < .001), lower headache frequency (10.5 ± 10.3 headaches/month vs 15.0 ± 11.7 headaches/month, P < .001), higher rate of episodic vs chronic migraine (67% vs 58.7%, P < .001), and higher rates of paternal migraine (24.1% vs 10.1%, P < .001), migraine in both parents (9.3% vs 3.1%, P = .007), and migraine in either parent (57.5% vs 45.5%, P = .02). CONCLUSIONS: The higher rate of vomiting in the younger patients and the patients with awakening pain may be explained by a common underlying pathogenetic mechanism of vomiting and migraine involving autonomic nerve dysfunction/immaturity. The association of vomiting with parental migraine points to a genetic component of vomiting and migraine. It should be noted that some of the findings may simply reflect referral patterns in the tertiary clinic.

Comparison of comorbidities of migraine and tension headache in a pediatric headache clinic.

Objective To compare comorbidities between migraine and tension headache in patients treated in a tertiary pediatric headache clinic. Methods Files of patients with migraine or tension headache attending a pediatric headache clinic were retrospectively reviewed for the presence of organic comorbidities. Additionally, patients were screened with the self-report Strengths and Difficulties Questionnaire to identify nonorganic comorbidities. If necessary, patients were referred to a pediatric psychiatrist, psychologist or social worker for further evaluation. Results The study cohort comprised 401 patients: 200 with migraine and 201 with tension headache. The main organic comorbidities were atopic disease, asthma, and first-reported iron-deficiency anemia; all occurred with statistical significance more often with migraine than with tension headache (Familial Mediterranean fever was six times more frequent in the migraine group than in the tension headache group, but the difference was not statistically significant. Nonorganic comorbidities (psychiatric, social stressors) were associated significantly more often with tension headache than with migraine (48.3% versus 33%; p = 0.03). Conclusions Children and adolescents with migraine or tension headache treated in a dedicated clinic have high rates of organic and nonorganic comorbidities. In this setting, patients with migraine have significantly more organic comorbidities, and patients with tension headache, significantly more nonorganic comorbidities.

Factors Influencing Response to Pharmacologic Treatment of Migraine in a Pediatric Headache Clinic.

OBJECTIVE: The responses of different patients to the same drug may vary as a consequence of biologic, psychosocial, and genetic differences. The aim of this study was to identify clinical factors associated with a response to pharmacologic treatment in pediatric patients with migraine. METHODS: The medical files of patients with migraine attending the headache clinic of a tertiary pediatric medical center in 2010-2015 were reviewed. The children and parents (or only the parents if the child was very young) completed the International Headache Society-based questionnaire. Patients were treated with at least one of the following medications: propranolol, amitriptyline, topiramate. Response to treatment was rated as no change in migraine pattern (grade 1) or a decrease in migraine attack frequency per month by at least 50% (grade 2) or at least 75% (grade 3). The highest-grade response to any pharmacologic treatment was defined as the best clinical response. RESULTS: The study group included 248 patients of mean age 12.71 ± 3.04 years. A grade 3 best clinical response was significantly associated with a positive maternal history of migraine, younger age at treatment onset, lower frequency of headache attacks per month, postpubertal children had a significantly lower rate of grade 3 response than prepubertal children (P < .05). Analysis of the association of overuse of medication and treatment response achieved a P value equal to .05. CONCLUSIONS: Several background and clinical factors are identified that may predispose children with migraine to respond better to pharmacologic treatment. Clinicians who see children with migraine in a pediatric headache clinic setting should consider these factors before initiating a treatment program.

Long-term Follow-up of Observation-Only Management of Nontuberculous Mycobacterial Lymphadenitis.

A total of 21 children with clinically and microbiologically proven craniofacial nontuberculous mycobacterial lymphadenitis managed by observation only at a tertiary medical center in 1993-2005 were evaluated for scar parameters at least 2 years after diagnosis. Parents completed a satisfaction questionnaire. Median follow-up time from presentation was 6.8 years (range = 2.3-16.9 years). In all, 18 patients showed scar formation, for a total of 26 scars; 21 scars (81%) had a maximal length of ≤3 cm. Vascularity was normal in 20 scars (77%), and pigmentation was normal in 18 (69%); 21 scars (81%) had a normal to only mildly uneven surface. Although 8 parents (44%) reported that the presence of the scar disturbed them, all responders but one (94%) expressed overall contentment of observation only as a conceivable management alternative. In conclusion, an observation-only approach to craniofacial nontuberculous mycobacterial lymphadenitis is associated with an acceptable outcome and may be an alternative to patients who wish to avoid surgery.

Lenticulostriated vasculopathy is a high-risk marker for hearing loss in congenital cytomegalovirus infections.

AIM: This study investigated the relationship between lenticulostriated vasculopathy (LSV) and hearing loss in 141 infants with congenital cytomegalovirus (cCMV) infection. METHODS: We included all infants with cCMV infection who were followed in our clinic for more than a year with only LSV signs of brain involvement on initial brain ultrasound. Group one comprised 13 infants with no hearing impairment at birth who were not treated with gan/valganciclovir during 2006-2009. Group two was 51 infants with LSV and no hearing impairment who had been treated since mid-2009. Group three was 25 infants born with LSV and hearing loss, who had been treated from birth. Group four was 52 control infants born during the same period with asymptomatic cCMV. Hearing tests were performed during the neonatal period and every four to six months until four years of age. RESULTS: Hearing deterioration was more extensive in group one (85%) than in group two (0%, p < 0.001) and the asymptomatic group (10%, p < 0.001) and occurred more often in group four (10%) than in group two (0%, p = 0.008). CONCLUSION: Lenticulostriated vasculopathy was common in infants with cCMV infection and may serve as a sign of central nervous system involvement and further hearing deterioration. Antiviral treatment may be prudent in such infants.

Association of pediatric obesity and migraine with comparison to tension headache and samples from other countries.

The link between body weight and headache has hardly been examined in children. The aim was to evaluate the association of obesity and migraine in selected pediatric patients and compare the findings with the literature. Data on clinical symptoms, headache type, and body mass index standard deviation score were derived from the medical files of 245 patients with migraine and 87 with tension headache. Comparison of the 3 subgroups of migraine patients of normal weight, overweight, and obese with the corresponding body mass index standard deviation score subgroups of patients with tension-type headache yielded no statistically significant differences in frequency of headache attacks per month, or duration of headache attacks in hours. These results call into question earlier reports linking headache and obesity in children. Differences in findings between our study and those in the literature highlight several factors that should be addressed in further studies. A larger sample size may reveal more significant results.

Phenotypic variability in patients with fanconi-bickel syndrome with identical mutations.

OBJECTIVE: To describe the phenotypic features of an ethnically homogenous group of patients with Fanconi-Bickel syndrome harboring the p.R310X mutation. METHODS: The study group consisted of eight patients from a single Bedouin family with clinically and molecularly diagnosed Fanconi-Bickel syndrome who had been followed at the same tertiary medical center for 8 years or more. All were homozygous for the p.R310X mutation. The medical files were reviewed for presenting signs and symptoms, laboratory and imaging findings, treatment regimens, and disease severity over time. RESULTS: Seven patients were diagnosed at our center before age 1 year, and one transferred from another center at age 16 years. Most patients presented with failure to thrive and/or hepatomegaly. All had short stature and doll-like facies. Most had biochemical abnormalities. Evaluation of the long-term findings revealed a wide spectrum of disease severity according to the following parameters: growth patterns, maximal electrolyte replacement therapy, skeletal and renal complications, frequency of follow-up visits, and hospitalizations for disease exacerbations. There was no apparent association of the clinical picture at presentation and later disease severity. CONCLUSION: Fanconi-Bickel syndrome has a broad phenotypic variability in patients harboring the same homozygous p.R301X mutation. This finding might be explained by genetic elements such as modifier genes and epigenetic factors, as well as the effects of still-undetermined environmental and nutritional factors.

Occipital and craniocervical pain and brain MRI in children with migraine.

BACKGROUND: Both cervical and occipital pain has been reported in pediatric patients with migraine. There are no descriptions of anatomical changes on conventional brain magnetic resonance imaging that can explain the pathophysiology of headache with cervical and occipital pain in this age group. Our aim was to evaluate the frequency of cervical and occipital pain in children and adolescents with migraine as opposed to other types of headache and to seek corresponding anatomic abnormalities on brain magnetic resonance imaging. METHODS: The cohort included 194 patients with headache attending the ambulatory headache clinic of a pediatric tertiary medical center. Data were collected by medical file review and revision of conventional magnetic resonance scans. RESULTS: Patients were divided into two groups: migraine headache (n = 125) and other types of headache (n = 69). Occipital pain was reported by 16.4% of the patients and cervical pain by 4.1%; neither type of pain was characteristic of migraine headache in particular. Brain magnetic resonance imaging did not show any anatomic changes specific to migraine or other headache types, regardless of the presence of occipital or cervical pain. CONCLUSIONS: Occipital and cervical pain are not characteristic symptoms of any headache group in the pediatric age group, and their presence or absence does not correspond to changes on conventional brain magnetic resonance imaging.

Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency.

The E3 subunit of the pyruvate dehydrogenase complex (dihydrolipoamide dehydrogenase/dihydrolipoyl dehydrogenase/DLD/lipoamide dehydrogenase/LAD), is a mitochondrial matrix enzyme and also a part of the branched-chain ketoacid dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. DLD deficiency (MIM #246900), is relatively frequent in the Ashkenazi Jewish population but occurs in other populations as well. Early diagnosis is important to prevent episodes of metabolic decompensation, liver failure, and encephalopathy. The clinical presentations are varied and may include Reye-like syndrome, hepatic failure, myopathy, and myoglobinuria. Laboratory markers, such as elevated urinary alpha-ketoglutarate, blood pyruvate, lactate, and ammonia, are mostly nonspecific and not always present, making the diagnosis difficult. Since we observed elevated plasma citrulline levels in a number of confirmed cases, we retrospectively examined the value of citrulline as a biochemical marker for DLD deficiency. Data was gathered from the files of 17 pediatric patients with DLD deficiency, confirmed by enzymatic and genetic analysis. The control group included 19 patients in whom urea cycle defects were ruled out but DLD deficiency was suspected. Seven of the DLD-deficient patients presented with elevated plasma citrulline levels (median value 205 µM, range 59-282 µM) (normal range 1-45 µM) while none in the control patient group. In five patients, elevated citrulline was associated with elevated plasma glutamine and metabolic acidosis. Interestingly, elevated plasma citrulline was associated with the common G229C mutation. In conclusion, we suggest that elevated plasma citrulline in the absence of urea cycle defects warrants an investigation for DLD deficiency.

McArdle disease: a novel mutation in Jewish families from the Caucasus region.

McArdle disease is caused by a myophosphorylase deficiency consequent to defects in the PYGM gene. A minority of the over-133 known mutations are associated with ethnicity, occurring mainly in patients from western Europe, the United States, and Japan. We identified a novel mutation, c.632delG, in three unrelated families of Jewish descent originating from the Caucasus region. This possibly ethnicity-associated mutation can significantly facilitate the diagnosis in Jews of the Caucasus and contribute to genetic consultations.

Nonpharmacologic treatment of migraine with low-dose propranolol or amitriptyline.

This study evaluated the effectiveness of nonpharmacologic measures combined with low-dose propranolol or amitriptyline for treating severe pediatric migraine. Data were collected from the medical files of 118 patients (mean age, 12.54 ± 3.14 years S.D.). All were treated with nonpharmacologic measures. In addition, 93 children received propranolol (mean initial dose, 0.4 ± 0.17 mg/kg/day S.D.), and 25 received amitriptyline (mean initial dose, 0.26 ± 0.1 mg/kg/day S.D.). Twenty patients were switched from propranolol to amitriptyline during treatment. In both groups, headache frequency was reduced by >50% per month in ~80% of patients. Patients without aura responded significantly better to propranolol than patients with aura (P = 0.02). No significant difference was evident in response to pharmacologic treatment by migraine frequency or type (episodic chronic). No significant difference was evident in response to amitriptyline between patients with or without aura. The response rate was higher than previously reported for placebo. Low-dose propranolol and low-dose amitriptyline, when combined with nonpharmacologic measures, are equally effective in reducing the frequency of migraine in children. Propranolol is preferred because of its lower risk of side effects. An additive effect of nonpharmacologic measures may allow for a reduction in drug dose.

Long-term follow-up for ophthalmologic sequelae in children treated with corticosteroids for infantile spasms.

The aim of the study was to determine if early steroid treatment of infantile spasms is associated with ocular complications years after its termination. Twenty-five patients with infantile spasms who underwent prolonged treatment with intramuscular synthetic adrenocorticotropic hormone (ACTH) and oral prednisone were evaluated for ocular complications 2 to 33 years after treatment cessation. Patients were followed by an ophthalmic examination that included anterior and posterior segments and measurement of intraocular pressure. Intraocular pressure was normal bilaterally in all patients. Findings on anterior segment examination were unremarkable. On posterior segment examination, 3 patients had an increased cup/disc ratio with normal intraocular pressure. In 2 patients, the increased ratio was considered an anatomical variant. Posterior segment findings in 2 patients were attributed to their background disease. In conclusion, early treatment with high-dose synthetic adrenocorticotropic hormone and oral prednisone for infantile spasm is apparently not associated with a risk of occular complications on long-term follow-up.

Effect of high-dose glucocorticosteroid treatment for infantile spasms on quantitative bone parameters later in life.

This study evaluated possible long-term effects of prolonged high-dose glucocorticosteroid administration in infancy. Thirty patients (16 male, 14 female; age 4.8-33 years) who had completed treatment with adrenocorticotropic hormone (ACTH) followed by glucocorticoids for infantile spasms at a tertiary pediatric hospital at least 2 years previously were invited to undergo quantitative bone ultrasound. The mean speed of soundZ score was -1.085 ± 1.079 for the radius and -0.22 ± 1.19 for the tibia on the nondominant side (P = .0022). The difference from the reference mean (0) was statistically significant for the radius (P < .001). There were no significant differences in radial or tibial mean speed of soundZ scores by age (prepubertal versus pubertal/postpubertal). In conclusion, a high percentage of patients treated with glucocorticoids for infantile spasms have a low radial speed of soundZ score later in life. Long-term follow-up can help to prevent and treat impairments in bone density, especially in non-weight-bearing organs.

Is lenticulostriated vasculopathy a sign of central nervous system insult in infants with congenital CMV infection?

BACKGROUND: In previous studies, lenticulostriated vasculopathy (LSV) was detected in 0.4-5.8% of neonates who had undergone brain ultrasound studies during the neonatal period. Most infants were referred from neonatal intensive care units. Various clinical conditions were associated with LSV including intrauterine infections. OBJECTIVE: To investigate whether LSV as a single abnormal finding in neonates with congenital cytomegalovirus (CMV) infection is a sign of central nervous system (CNS) involvement. METHODS: Ultrasonographic and clinical data of all infants with congenital CMV infection, followed in our hospital, were collected. All infants with symptomatic congenital CMV infection and CNS involvement were treated with ganciclovir for 6 weeks, followed by valganciclovir until the age of 1 year. Infants with asymptomatic as well as symptomatic infections were followed up with brainstem evoked response and behavioural studies every 4 months until 4 years of age. RESULTS: 92 infants diagnosed with congenital CMV infection were included in the study. In 50 (54.3%) infants, LSV was detected on initial brain ultrasound. Among these patients, 21 (42%) infants had other ultrasonographic findings consistent with congenital CMV infection; 11 (22%) had other symptoms of CNS involvement and in 18 (36%) cases the only abnormal finding was LSV. In 9 of the 18 infants with LSV as the only finding on initial examination, antiviral therapy was not started. Hearing deterioration developed in all nine infants between ages 4 and 34 months. Subsequent to these cases, the authors modified their therapy protocol and began treating congenital CMV infants with only LSV. 9 infants were treated and all maintained normal hearing after 8-27 months of follow-up (p<0.01). CONCLUSIONS: LSV is a common finding in infants with symptomatic congenital CMV infection and is a sign of CNS involvement. Moreover, LSV is a possible marker of high risk for sensorineural hearing loss in infants with congenital CMV infection.

Breast asymmetry during adolescence: physiologic and non-physiologic causes.

BACKGROUND: Pathologic breast conditions are rare in childhood and adolescence. The spectrum of breast disease in the pediatric age group is different from that in adults, and most lesions are benign. OBJECTIVES: To describe the causes and characteristics of breast asymmetry in adolescents with normal endocrine profiles and sexual development. METHODS: The files of patients with a diagnosis of breast asymmetry referred to a tertiary pediatric center from 1990 to 2007 were reviewed for history and findings on physical examination with or without imaging, treatment and outcome. RESULTS: Eleven patients aged 12.5 to 18 years were identified. The cause of the breast asymmetry was traced to unpreventable medical factors in eight patients (physiologic, Poland anomaly, scleroderma), preventable/iatrogenic factors in two patients (chest tissue biopsy, thoracic drain), and possible combined medical-iatrogenic factors in one patient (scoliosis treated with a body brace). All patients were referred for breast reconstruction after full breast development. CONCLUSIONS: Severe breast asymmetry in adolescence may be due to congenital factors, diseases involving the breast tissue, or to the effects of medical treatment, and may have severe adverse psychological and social implications. To prevent iatrogenic breast asymmetry, physicians should be made aware of the sensitivity of the breast tissue and should avoid unnecessary tests/procedures that involve the chest wall. In most cases a precise medical history and physical examination can differentiate between physiologic and non-physiologic causes.

Effectiveness of nonpharmacologic treatment for migraine in young children.

OBJECTIVE: To evaluate the effectiveness of nonpharmacologic treatment for migraine in children younger than age 6 years. BACKGROUND: The mean age of onset of migraine in children is 7.2 years for boys and 10.9 years for girls. Treatment consists of individually tailored pharmacologic and nonpharmacologic interventions. However, data on migraine management in preschoolers are very sparse. METHODS: Demographic, clinical, and outcome data were collected from the files of patients with migraine who attended a pediatric headache clinic. Only those treated by nonpharmacologic measures, namely, good sleep hygiene, diet free of food additives, and limited sun exposure, were included. Clinical factors and response to treatment were compared between children younger than 6 years and older children. RESULTS: Of the 92 children identified, 32 were younger than 6 years and 60 were older. There was no difference between the age groups in most of the demographic and clinical parameters. The younger group was characterized by a significantly lower frequency of migraine attacks and shorter disease duration (in months). Mean age of the patients with no response to treatment (grade 1) was 10.588 +/- 3.254 years; partial response (grade 2), 9.11 +/- 4.6 years; and complete response (grade 3), 8.11 +/- 3.93 years (P = .02). The percentage of patients with complete to partial response as opposed to no response was significantly higher in the younger group (P = .00075). CONCLUSION: As the primary option, conservative therapy for migraine appears to be more effective in children younger than 6 years than in older children, perhaps because of their shorter duration of disease until treatment and lower frequency of attacks.

[Nontuberculous mycobacterial lymphadenitis with an emerging pathogen and a novel management approach].

Nontuberculous mycobacterial infections in immunocompetent children usually presents as chronic lymphadenitis involving the neck and face. Mycobacterium avium complex is the most common pathogen, although recent series found Mycobacterium haemophilum, to be a major cause of chronic lymphadenitis in otherwise healthy children. The authors describe a 9-month-old baby who presented with a 4-month history of preauricular lymphadenitis. Mycobacterial culture yielded Mycobacterium haemophilum. A no-intervention approach was chosen. At the 6-month follow-up, the swelling had ameliorated and the skin showed a small scar with near-normal overlying skin color. A literature review of the clinical manifestations and diagnosis of Mycobacterium haemophilum lymphadenitis and of the different management options for nontuberculous mycobacterial lymphadenitis in otherwise healthy children is presented.

Chronic cheek lesions: an unusual manifestation of nontuberculous mycobacterial cevicofacial infection.

The characteristics of nontuberculous mycobacteria cheek lesions in 7 children were reviewed. The lesions usually presented as nontender erythematous nodules and were associated with a positive purified protein derivate tuberculin skin test. Mycobacterium haemophilum was isolated in 4 cases (57%) and Mycobacterium avium complex in 3 (43%). Cytology and imaging were noncontributory. Resolution was prolonged.

Management of nontuberculous mycobacteria-induced cervical lymphadenitis with observation alone.

BACKGROUND: Nontuberculous mycobacteria can cause a chronic localized cervicofacial lymphadenitis in immunocompetent children. The recommended treatment is total excision of the affected lymph node. The aim of this study was to describe our experience with an observational approach. METHODS: Children with chronic nontuberculous mycobacterial (NTM) cervical lymphadenitis, whose parents opted for conservative treatment, were followed at our center from 1990 to 2004. The diagnosis of NTM was based on mycobacterial culture of lymph node specimens obtained by fine needle aspiration. The clinical laboratory and follow-up data were documented. RESULTS: Ninety-two children with lymph node positive cultures of nontuberculous mycobacterium were included in the study. Mycobacterium avium complex and Mycobacterium hemophilum were isolated in 90% of the cultures. In most cases, the affected lymph nodes underwent violaceous changes with discharge of purulent material for 3-8 weeks. Total resolution was achieved within 6 months in 71% of patients and within 9-12 months in the remainder. At the 2-year follow-up, a skin-colored, flat scar in the region of the drainage was noted. There were no complications. CONCLUSIONS: We suggest that the observational approach can be effective for managing NTM lymphadenitis in immunocompetent children.