We read with great interest the paper by Shaw “Osteoporosis in pediatrics” (Arch. Dis. Child. Ed. Pract., December issue). The author doesn’t cite celiac disease as a specific cause of osteoporosis in children, although he correctly recommends celiac screening in case of suspected secondary osteoporosis.

A diminished bone mineral density with z score lower than -1.0 standard deviation (SD) can be found in up to 50% of children with celiac disease; more severe reduction of mineral density with z score lower than -2.5 SD is generally observed only in newly diagnosed children or in adults.[1] Moreover, celiac patients, including children, are at increased risk of hip fractures and fractures of any type.[2]

Osteoporosis in celiac disease may be due not only to malabsorption, but also to abnormalities in cytokine levels.[3] Increased levels of osteoclast-triggering cytokines, such as IL-1, IL-6 and TNFalfa, have in fact been found in untreated CD patients, while the level of inhibitory cytokines such as IL-18 and IL-12 may be lowered. Normalization of cytokines levels with a gluten-free diet may explain the increased bone mineral density observed in osteopenic celiac children, particularly under 4 years, while this effect is not so obvious in adults. [1, 4] As bone mineral density can be reduced both in symptomatic and in silent celiac disease, early diagnosis is important not only in order to achieve a normal bone mineral density, but also to prevent the onset of autoimmune conditions associated to celiac disease.[5]

In conclusion, osteopenia and osteoporosis may be the only manifestation of silent/latent celiac disease, leading to an increased risk of fractures. Given the high prevalence of celiac disease, and the effectiveness of a gluten-free diet in treating and preventing its complications, it is relevant to consider celiac disease in the differential diagnosis of osteoporosis in pediatrics.

References

1 Kalayci AG, Kansu A, Girgin N, et al. Bone mineral density and importance of a gluten free diet in patients with celiac disease in childhood. Pediatrics 2001;108:E89.

2 Ludvigsson JF, Michaelsson K, Ekbom A, et al. Coeliac disease and the risk of fractures – a general population based cohort study. Aliment Pharmacol Ther 2007;25:273-85.

3 Bernstein CN, Leslie WD. The pathophysiology of bone disease in gastrointestinal disease. Eur J Gastroenterol Hepatol 2003;15:857-64.

4 Tau C, Mautalen C, De Rosa S, et al. Bone mineral density in children with celiac disease. Effect of a gluten free diet. Eur J Clin Nutr 2006;60:358-63.

5 Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in chldren: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005;40:1-19.

Dear Editor,

Dr Roberts questions the point of treating warts and molluscum which are benign and will often spontaneously resolve, and expresses concern about discussing these methods of treatment at all. In terms of the former, I regret that I did not more explicitly state that the so-called "tincture of time" is, by far, the preferred method of treating these lesions. The focus of the review is on those cases where there is a compelling reason to seek further treatment, with emphasis on sorting through the vast (and often anecdotal) literature on these treatments.

As Dr Roberts notes, the consultant dermatologists carry a heavy load in the UK, and this is perhaps equally true in the US.[1] Ironically, it was the tremendous number of "emergency" consultations that are referred to our practice for warts and molluscum that prompted me to write this article. Many patients are referred by their pediatricians for warts and molluscum that have persisted or are spreading, causing a great deal of anxiety and frustration for all parties. Importantly, many of these patients express anger towards their pediatrician and frequently feel marginalized because they were told the lesions would go away without treatment. Sometimes, the children are ostracized from school, public pools or sporting events, adding psychological stress to the entire family.[2]

Much more concerning, however, is when doctors or the patients themselves feel compelled to treat these lesions and do so in ways that may cause harm. I specifically cautioned against using imiquimod for molluscum, for example, as I have seen many adverse effects when used for this purpose. I have seen patients apply powerful acids and create painful ulcers which scar, and have seen children traumatized by curettage without anesthesia of any sort. The secondary purpose of the paper, then, is to discuss these methods openly and without bias, so that if treatment is deemed necessary, there is some context and experience for choosing an appropriate treatment in a manner that is safe for the patient.

Drs Goodyear and Taibjee raise concern that I impugn evidence-based medicine (EBM). In fact, in my five-page paper with almost 50 references from the peer-reviewed literature including heavy reliance on the Cochrane Database, I sought to explore the area where there is not yet enough evidence to make easy rational choices about treatment of these skin diseases. Indeed, on the British Association of Dermatologists website, the only treatments that were given the strength of evidence D ("There is fair evidence to support the rejection of the use of the procedure") were oral cimetidine and homeopathy.[3] There were no treatments given strength of evidence E ("There is good evidence to support the rejection of the use of the prodedure"). In fact, two of the treatments I discussed (imiquidmod and heat treatment/balneotherapy) were deemed to have insufficient evidence at this time. As a strong proponent of EBM, I try to remain vigilant for the fallacy of argumentum ad ignorantiam in all its forms, which in this case might be best put: "absence of evidence is not evidence of absence."

In sum, I overwhelmingly agree with the comments of Drs Goodyear, Taibjee, and Roberts and appreciate the opportunity to put the review in a proper light.

References:

1. Tsang MW, Resneck JS Jr. Even patients with changing moles face long dermatology appointment wait-times: a study of simulated patient calls to dermatologists. J Am Acad Dermatol 2006;55(1):54-8.

2. Braue A, Ross G, Varigos G, et al. Epidemiology and impact of childhood molluscum contagiosum: a case series and critical review of the literature. Pediatr Dermatol 2005;22:287–94.

3. BAD.org.uk/healthcare/guidelines/cw.

Dear Editor,

We welcome the Education and Debate article on Toxic Shock Syndrome(1), which helps improve the profile of this potentially devastating disease and enhances diagnostic recognition.

It is however important to highlight some specific areas in prevention, diagnosis and therapy which are not fully discussed within this review.

As the authors state, early diagnosis can be difficult but is crucial to improving prompt intervention and therapy. Case definitions are complex but are well established and importantly differentiate staphylococcal from streptococcal toxic shock (2). It is important to realise that streptococcal toxic shock does not always present with a rash, nor is pyrexia included within the case definition, although isolation of GAS is required. Rash is therefore not an essential diagnostic criteria when assessing children initially before the results of cultures are known.

Prevention is important and there was little expansion on the role of prophylactic antibiotics in burns which has gathering evidence for efficacy in the prevention of toxic shock syndrome(8,9).

The authors state that effective antitoxin therapy is considered an essential part of management, but describe only the potential for antitoxin blocking antibody. There is however a growing literature on the specific antitoxin effect of antibiotics such as clindamycin, aminoglycosides and linezolid which have been shown to reduce TSST 1 and streptococcal exotoxin A (3,4,5). Clindamycin is now an accepted and recommended adjunctive therapy for both staphylococcal and streptococcal toxic shock (2-5).

Inhibition of T cell activation by blocking or inactivating staphylococcal and streptococcal superantigens is theoretically attractive (6). Its use in streptococcal toxic shock has suggested benefit, (statistically significant results perhaps prevented by early termination of this study because of slow recruitment) (7), but there have been no such studies with FFP, which the authors suggest is useful. Although specific anti-toxin antibody may be detected in FFP, the level of this antibody is likely to be significantly lower than in IVIG and hence passive immunity may not be achieved. There is no other evidence base for FFP apart from the authors’ experience, and although it may well have been successful for the authors is not consistent with other accepted guidelines (2).

Management guidelines for Toxic shock are specifically outlined by the American Academy of Pediatrics (2) as follows:

• Fluid management to maintain adequate venous return and cardiac filling pressures to prevent end organ damage.
• Anticipatory management of multi system organ failure.
• Parental antimicrobial therapy at maximal doses for age.
o Kill organism with bactericidal cell wall inhibitor (e.g. beta-lactamase resistant antistaphylococcal antimicrobials).
o Stop enzyme, toxin, or cytokine production with protein synthesis inhibitor (e.g. clindamycin).
• Intravenous immune globulin may be considered for an infection refractory to several hours of aggressive therapy, in the presence of an undrainable focus, or where there is persistent oliguria with pulmonary oedema.

The guidelines for the management of toxic shock syndrome should include Clindamycin as an adjunctive treatment and IVIG where necessary. FFP should not be used as a specific anti-toxin (without an evidence base) but may be useful as part of volume expansion management.

References:

1. A Young, K Thornton. Toxic shock syndrome in burns: diagnosis and management. Arch Dis Child Educ Pract Ed 2007;92:ep97-ep100.

2. American Academy of Pediatrics [Toxic Shock Syndrome]. In: Pickering LK,ed. 2000 Red Book: Report of the Committee on Infectious Diseases. 25th edition. Elk Grove Village, IL: American Academy of Pediatrics;2000:p580.

3. Chuang et al. Toxic shock syndrome in children epidemiologic, pathogenis, and management. Pediatric drugs. 2005;7(1):11-25.

4. Coyle E.A, Cha R, Rybak M J. Influences of linezolid, penicillin and clindamycin alone and in combination on streptococcal pyrogenic ExotoxinA release. Antimicrobial Agents and Chemotherapy. 2003;47(5);1752-1755.

5. Annane D, Clair B, Salomon J. Managing toxic shock syndrome with antibiotics. Expert Opin. Pharmacother. 2004;5(8):1701-1709.

6. Darenberg J et al. Differences in potency of Intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. CID. 2004:38:836-842.

7. Darenberg J et al. Intravenous immunoglobulin G therapy and streptococcal toxic shock syndrome. CID. 2003;37:333-40.

8. Abid Rashid, Alastair P. Brown, Khalid Khan. On the use of prophylactic antibiotics in prevention of toxic shock syndrome. Burns 31 (2005) 981–985.

9. Edwards-Jones V, Dawson MM, Childs C. A survey into toxic shock syndrome (TSS) in UK burns units. Burns 26 (2000) :323–33.

Dear Editor,

Keady S (1) provides some updated guidelines on the drug treatment of gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD). However, in order to give clear management guidelines, we believe that the review should have first addressed the definition of GOR (ie, physiological) versus GORD (ie, pathological). In fact, the results of a recent survey on the knowledge, attitudes and practice styles of North American Pediatricians regarding GOR show that still many infants are inappropriately treated for GORD when all they have is physiological GOR (2). The first important goal of future educational efforts should be therefore directed to avoid overtreatment of “happy spitters” (ie, GOR). Second, in his conclusions Keaty correctly underlines that “the majority of drugs used have limited robust data supporting their use”. However, some evidence from randomised controlled trials (RCTs) is now available but it is not clearly reflected by the practice guidelines Keaty suggested. An example of this is the use of prokinetic drugs (domperidone or erythromycin), in association with an appropriate acid suppressant, recommended for the treatment of moderate o severe GORD. A recent systematic review of RCTs showed that, even if from the limited evidence available (the 4 RCTs named by the same Keaty), domperidone does not appear to be more effective than placebo in reducing symptoms of GOR and GORD (3). Given the usually benign nature of GOR, the widespread use of prokinetic drugs is therefore not indicated. In severe cases of GORD, where medical management is required, available evidence suggest that domperidone is yet not indicated. Its use may be re-considered if further data was to provide robust evidence of a favourable benefit-risk profile. The overall variability in practice style and lack of conformity to Naspghan GORD guidelines (4) merit further efforts in education and in terms of guideline availability based on the results of good clinical trials with relevant outcome measures.

Federico Marchetti, Jenny Bua, Alessandro Ventura

Department of Paediatrics, Institute of Child Health, IRCCS Burlo Garofolo, Trieste, Italy

e-mail: fedemarche@tin.it

Competing interests: None declared

References:

1.Keady S. Update on drugs for gastro-oesophageal reflux disease. Arch Dis Child Educ Pract 2007;92:ep114-ep118

2.Diaz DM, Winter HS, Colletti RB, Ferry GD, Rudolph CD, Czinn SJ, Cochran W, Gold BD; NASPGHAN/CDHNF Scientific Advisory Board. Knowledge, attitudes and practice styles of North American pediatricians regarding gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2007;45(1):56-64.

3.Pritchard DS, Baber N, Stephenson T. Should domperidone be used for the treatment of gastro-oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old. Br J Clin pharmacol 2005;59(6):725-9

4.Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children. Recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 2001;32 (Suppl 2) :S1–S31