Dear Sir,

We read with interest the review on ‘The paediatrician and the management of common gynaecological conditions’ (1). This is an important topic but we have concerns about incorrect information in this paper with respect to vulval disorders. Most vulval conditions are dermatological rather than gynaecological and the involvement of a dermatologist in the management of these children is vital. The breadth of paediatric vulval disease is not reflected in this paper including the concept of vulval presentation of various skin conditions (eg. psoriasis, chronic bullous dermatosis of childhood, erythema multiforme) and the need to examine the rest of the skin including the hair, nails and mucosa.

There appears to be some confusion within the article, for example, a vaginal discharge is not a vulval disorder. While a discharge can lead to a vulvitis, the two problems of vaginitis and vulvitis should be distinguished as the investigation and management of each is very different.

The commonest condition seen in children presenting with vulval symptoms is an irritant dermatitis which is not specifically mentioned in the section on vulval irritation. This is often seen in those with a background of atopy and requires emollients and a mild topical steroid application intermittently with good hygiene measures. Other important disorders such as Lipschutz ulcers and genital warts have been omitted.

However, our major concerns relate to the section on lichen sclerosus (LS). This is an important condition which is often under-recognized or with significant delay in diagnosis. The references used are old and not original. The major symptom is itch which is not always synonymous with irritation. One of the frequent presenting symptoms of LS in children is constipation which again is not mentioned. LS should always be treated, even if asymptomatic as it is a disease that can lead to permanent anatomical change with functional sequelae. Detailed guidelines for the management of LS have been published recently (2) and were agreed by the Royal College of Paediatrics and Child Health in the consultation process. All the evidence shows that a 3 month induction regimen of an ultra-potent topical steroid is the first line treatment (3). Thereafter, the management is individualized to maintain control of symptoms and signs (4). The management outlined in this review is incorrect and gives the wrong message. It should be corrected as otherwise it will lead to undertreatment and its potential consequences. As with all vulval disorders, these children should be under the care of those experienced in the management of this condition and should receive dermatological input as part of the multi-disciplinary team.

FM Lewis MD FRCP, St John’s Institute of Dermatology, Guy’s & St Thomas’ Hospital, London
SS Velangi FRCP Queen Elizabeth University Hospital, Birmingham
SM Taibjee MB BCh BMedSci MRCPCH CCT Derm DipRCPath (Dermatopathology) Dorset County Hospital, Dorchester

References

1. Ritchie JK et al. The paediatrician and the management of common gynaecological conditions. Arch Dis Child 2018;108:703-6

2. Lewis FM Tatnall FM, Velangi SS et al. British Association of Dermatologists guidelines for the management of lichen sclerosus, 2018. Br J Dermatol 2018;178:839-53.

3. Mashayeki S, Flohr C, Lewis FM. The treatment of vulval lichen sclerosus in prepubertal girls: a critically appraised topic. Br J Dermatol 2017;176:307-16.

4. Ellis E, Fischer G. Prepubertal-onset vulvar lichen sclerosus: the importance of maintenance therapy in long-term outcomes. Ped Dermatol 2015:32:461-7.

I was interested to read the articles in this month’s journal exploring the difficulties of end of life decisions when parents and their doctors cannot agree.(1–3) These articles reflect the global media attention focused upon several recent tragic cases in the UK, where differences in view between parents and the clinical team led to confrontation and an unfolding tragedy in the public arena. Whilst all these articles describe the complexity they offer little in terms of solutions. Is it possible to prevent future cases from degenerating into public dispute, or is it an inevitable consequence of modern medicine? Have we advanced to a point where children that would have succumbed now live, and so the focus of care has shifted towards how they live rather than if they live or die?

At least part of the solution should be a shift in focus shift toward prevention of conflict in these high stakes clinical areas rather than finding a remedy once conflict has occurred. This is not just about being better at communicating with families. Conflict prevention will require cultural change, the identification of early warning signs and the use of mediation to facilitate communication between parents and doctors at an early stage.

Communication is not just about what we say, but about how we act and the social networks that we live and work in. It was interesting that there was also an article on Family Integrated Care in the same issue of the journal (4). Patel and colleagues describe a new way of working in intensive care medicine, where parents are integrated into the clinical team as primary caregivers. They describe how cultural changes to clinical practice enhance the wellbeing of parents and reduce length of stay of their new-borns. Parental integration will surely improve communication between parents and staff. It reduces barriers to effective communication and creates a shared problem rather than adopting sides.

Despite everyone’s best efforts, there will be times when dissatisfaction and conflict arise. To prevent communication breakdown we should identify risk factors within the situation that would lead to early intervention. Forbat et al identified three distinct phases of escalation in paediatric conflicts from mild, through, moderate to severe.(5) The mild stage focussed on conflict triggers, for example, the inappropriate use of language, conflicting messages given to parents by clinical staff, staff making assumptions about parents and a history of previous unresolved conflict. Training clinical staff to recognise conflict early and use mediation skills to de-escalate and resolve it is another intervention. Six month follow up of a cohort of staff trained in one tertiary children’s hospital reported that 57% of respondents had experienced conflict in the six months following the training. Of these, 91% reported that the training had enabled them to de-escalate the conflict.(6) Formal testing of a framework for the early recognition and management of conflicts between families and health professionals is being undertaken by four tertiary hospitals in the UK later this year.

Only after these foundations are in place, where parents are empowered as part of the clinical team, and an open and safe environment for communication already exists, that local hospital review panels and clinical ethics committees and the courts may be able to help when complex clinical decisions need to be considered. These panels should be introduced as part of the wider clinical team. Doctors and parents should approach them together as a united front to listen to their deliberations.

It is vital that we learn how to prevent these high-profile cases from occurring again. There are no winners or losers in these situations, only victims and casualties: parents whose chance of coping with bereavement has been broken, and a career curtailing event for the doctors and nurses who cared for them. When parents and doctors are in conflict, once sides have been drawn the battle is lost. Changing the way that we work with families, mediation as routine practice, and the early identification of the warning signs of conflict is the only way to prevent this from happening again.

References

1. Wallis C. When paediatricians and families can’t agree. Arch Dis Child. 2018 May;103(5):413–4.
2. Wheeler R. Response to “When paediatricians and families can”t agree’. Arch Dis Child. 2018 May;103(5):410–1.
3. Lagercrantz H. Observations on the case of Charlie Gard. Arch Dis Child. 2018 May;103(5):409–10.
4. Patel N, Ballantyne A, Bowker G, Weightman J, Weightman S, Helping Us Grow Group (HUGG). Family Integrated Care: changing the culture in the neonatal unit. Arch Dis Child. 2018 May;103(5):415–9.
5. Forbat L, Teuten B, Barclay S. Conflict escalation in paediatric services: findings from a qualitative study. Arch Dis Child. 2015 Aug;100(8):769–73.
6. Forbat L, Simons J, Sayer C, Davies M, Barclay S. Training paediatric healthcare staff in recognising, understanding and managing conflict with patients and families: findings from a survey on immediate and. Arch Dis Child. 2017 Mar;102(3):250–4.

I read with great interest the article titled “Off-label use of tacrolimus in children with Henoch-Schönlein purpura nephritis: a pilot study” by Zhang et al.(1). To my great astonishment the authors did not discuss any of the studies published on the use of another calcineurin inhibitor Cyclosporine A (CyA)  in the treatment of Henoch Schönlein purpura in children.

In the first chapter of the discussion section they refer to our report where we compared methylprednisolone pulse treatment (MP) and CyA in a randomized trial (2) stating that “Remission was achieved slowly and only in 53% of patients with methylprednisolone” (1).

I would like to draw the readers´s attention to the fact that in the same paper we showed that another calcineurin inhibitor i.e. CyA was by no means inferior to MP for the treatment of severe HSN (2). Indeed, CyA was even more efficacious than MP, since remission was achieved within 3 months in all CyA-treated patients (N=11) compared to 54% (7/13) in MP group (p=0.016). All the CyA treated patients responded to the treatment with no need for additional immunosuppressive therapy. In contrast, in MP group 6/13 (46%) needed additional immunosuppressive treatment. The remission rates in the MP treated patients were 85% (11/13) and 77% (10/13) after 1 and 2 years, respectively in contrast to 100 % in CyA-treated patients. The renal survival rate in the CyA group was 100%, as against 85% in the MP group (2). Several reports have shown that CyA is effective also as a rescue therapy for Henoch Schönlein nephritis when other treatments have failed (3-5). Faul et al. have suggested that the beneficial effect of CyA on proteinuria is not dependent on T-cell function, but rather results from stabilization of the actin cytoskeleton in the kidney podocytes (6).

REFERENCES

1. Zhang D-F, Hao G-X, Li C-Z et.al Off-label use of tacrolimus in children with Henoch-Schönlein purpura nephritis: a pilot study. e-pub http://dx.doi.org/10.1136/archdischild-2017-313788.

2. Jauhola O, Ronkainen J,Autio-Harmainen H, et al. . Cyclosporine A vs methylprednisolone for Henoch-Schönlein nephritis: a randomized trial. Pediatr Nephrol 2011;26:2159-66.

doi:10.1007/s00467-011-1919-5

3. Ronkainen J, Autio-Harmainen J, Nuutinen M. Cyclosporin A for treatment of severe Henoch-Schönlein glomerulonephritis. Pediatr Nephrol 2002;18:1138-42.

4. Someya T, Kaneko K, Fujinaga S, Ohtaki R, Hira M, Yamashiro Y. Cyclosporine A for heavy proteinuria in a child with Henoch-Schönlein purpura nephritis. Pediatr Int 2004;46:111-3.

5. Park J, Won S, Shin J, Yim H, Pai K (2010) Cyclosporin A therapy for Henoch-Schönlein nephritis with nephrotic-range proteinuria. Pediatr Nephrol 2010;26:411-7.

6. Faul C, Donnelly M, Merscher-Gomez S et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008;14:931-938.

I would like to thank Professor Mitch Blair for his valuable input and bringing up the issue of considering symptoms onset when interpreting point-of-care test results in acute care settings. Recognizing serious infection in children can be challenging, especially at disease onset when the severity of the infection is unclear. Although the choice of biomarker is pivotal in the risk assessment of acutely ill children guided by the point-of-care test result, we had very good rationale to choose C-reactive protein (CRP) as our preferred test.

Previous research:
CRP and procalcitonin were identified as the best inflammatory markers for serious infections in children to date in a systematic review, which only identified studies from hospital settings.[1] A CRP <20mg/L and procalcitonin <0.5ng/mL significantly reduce the risk of missing a serious infection in children. Our recent study on point-of-care (POC) CRP in primary care found an even lower threshold of 5mg/L to rule out serious infection in those children, probably due to the early presentation in primary care, when the inflammatory response is still developing, which indeed confirms the importance of setting.[2]
However, as shown in Figure 6 of the paper by Van den Bruel et al., C-reactive protein and procalcitonin had comparable diagnostic accuracy in the systematic review, as the shape of the curves was roughly similar and the confidence intervals were largely overlapping.[1]

Practical issues:
At the time of study onset, reliable POC tests were available for CRP only, providing test results within 4 minutes.[3, 4] As mentioned by Professor Blair in his e-letter, other tests such as the Brahms PCT-Q, a semi-quantitative point-of-care procalcitonin test, was available at the time, but required additional manipulation of the sample (centrifugation needed to obtain serum or plasma), a sample volume of 200µL (which was 133 times the volume used in the CRP point-of-care test (merely 1.5 µL, roughly a small drop of blood, especially useful in children)) and an incubation period of at least 30 minutes, which would not be manageable within a single acute care consultation. Therefore, it was not deemed suitable for application in our trial.

Study characteristics & findings:
In the present study, we only included children who were not referred by their general practitioner. Taking into account the organization of healthcare services in Belgium, children and parents may present to A&E directly or a consultant paediatrician of their choice, without the need for a letter of referral. This might explain why some children presented at an early stage of their illness to A&E services, potentially reducing the difference in patient spectrum between GP and hospital paediatric settings.
Furthermore, we found that children with a CRP between 20-75mg/L, should be assessed on seven features, including fever duration <1 day, which reflects the effect of disease onset on the CRP level.
In this particular CRP range, children could still have a serious infection if fever was only present for 1 day.

Conclusion:
Procalcitonin has been introduced as an earlier and more accurate diagnostic markers than currently available tests, however evidence of superior clinical accuracy in diagnosing serious infection in children in ambulatory care is still lacking.
I agree with Professor Blair that further prospective studies are needed to compare the clinical effectiveness of using point-of-care CRP and procalcitonin to guide clinical assessment in acute paediatric care.

REFERENCES

1. Van den Bruel A, Thompson M, Haj-Hassan T, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 2011;342:d3082
2. Verbakel JY, Lemiengre MB, De Burghgraeve T, et al. Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial. BMC Med. 2016;14(1):131 doi: 10.1186/s12916-016-0679-2published Online First: Epub Date]|.
3. Minnaard MC, van de Pol AC, Broekhuizen BD, et al. Analytical performance, agreement and user-friendliness of five C-reactive protein point-of-care tests. Scand. J. Clin. Lab. Invest. 2013;73(8):627-34 doi: 10.3109/00365513.2013.841985published Online First: Epub Date]|.
4. Verbakel JY, Aertgeerts B, Lemiengre MB, De Sutter A, Bullens DM, Buntinx F. Analytical accuracy and user-friendliness of the Afinion point-of-care CRP test. J. Clin. Pathol. 2014;67:83 - 86