*"It doesn't matter if the cat is black or white as long as it catches
mice."*

*Chinese Proverb*

This a page for sharing "what works" as seen in the published literature
as well as what is done at sites that care for American Indian/Alaskan
Native children. If you have any suggestions, comments or questions
please contact Steve Holve, MD, Chief Clinical Consultant in Pediatrics
at sholve@tcimc.ihs.gov

IHS Child Health Notes

**November 2007**

# Quote of the month

*"There are no answers, only stories."*\
Garrsion Keillor

**Guest Editorial**

**Challenges in Pediatric Rheumatic Disease: Special Issues with Native
Children**

James N. Jarvis, M.D.[^1] Dept. of Pediatrics, University of Oklahoma
College of Medicine, Oklahoma City, OK 73104

You've probably heard this dozens of times before, "This might be an
autoimmune disease. Order an ANA and a rheumatoid factor." It's a common
occurrence on adult medicine wards, and all too common in pediatrics as
well. It probably stems from the fact that, until recently, very few
medical schools had a pediatric rheumatologist; a third of the medical
schools in the United States still don't have one.[^2] Thus,
pediatricians have had to undertake their evaluations of children with
suspected rheumatic disease or musculoskeletal complaints using models
derived from adult medicine. One of the most important advances in
pediatric rheumatology over the past 15 years, and the one that has
received the least attention, I think, has been the growing body of
research that has shown just how inappropriate those models are for the
evaluation of children with musculoskeletal complaints and/or suspected
rheumatic disease.

Perhaps the most surprising finding has been the documentation that
isolated musculoskeletal pain is almost never the complaint with which
children with arthritis present to their primary care physicians. In a
retrospective study of 414 children evaluated at a university-based
pediatric rheumatology clinic, McGhee and colleagues[^3] demonstrated
that not a single child among 76 diagnosed with juvenile rheumatoid
arthritis (JRA) presented with a chief complaint of isolated
musculoskeletal pain. Rather, children with JRA invariably presented
with joint swelling and/or gait disturbance as their primary complaint.
The gait disturbance, when present, was typically better with activity
and worse with rest, exactly the opposite of what one finds in
mechanical musculoskeletal pain syndromes. Here in Oklahoma, we have
found that cultural considerations reinforce the absence of pain as a
common presenting complaint of children with chronic arthritis. Based on
these data, it is safe to make the cautious generalization that *if a
child is complaining of musculoskeletal pain, chronic forms of arthritis
can safely be excluded from the differential diagnosis, particularly if
the child has an otherwise normal physical exam*.

There is an exception to this rule, and the exception is highly relevant
to "Indian Country." Children with spondyloarthopathy (e.g., ankylosing
spondylitis), a form of arthritis common in Native American boys and
girls,[^4] frequently present hip isolated hip pain (low back pain is
seldom a part of the clinical presentation of spondyloarthopathy in
children). In these cases, the pain is quire typical of that found in
other forms of synovitis: most prominent after periods of inactivity.

This is the point where primary care providers like to ask, "OK, if I
consider one of these diagnoses, what tests do I order?" Unfortunately,
your choices are pretty slim. For example, children with chronic
polyarthritis, unlike adults, seldom express IgM-rheumatoid factor
(IgM-RF) detected on conventional latex agglutination assays.[^5] In
1986, Eichenfield and colleagues systematically examined the clinical
utility of IgM-RF testing in children.[^6] In that study, IgM-RF tests
were positive in only 4.8% of 426 children tested. The test was negative
in 95 children with JRA, giving it a poor negative predictive value as a
screening test for arthritis. Furthermore only 5 of the 11 children who
tested positive had rheumatoid arthritis, and, in each case, the
positive test added no additional value in establishing the diagnosis.
"Testing for rheumatoid factor is a poor screening procedure for
juvenile rheumatoid arthritis in the general situations in which it is
more likely to be requested..." This is a conservative statement, and it
is just as reasonable, based on these data, to state categorically that
*there is no reason to request a rheumatoid factor assay as a diagnostic
test on any child at any time*. This sweeping statement does not take
into account the higher prevalence of RF-positive disease in African
American[^7] and Native American[^8] children and in children from the
Indian subcontinent.[^9] Until we have better population-specific data,
this test should be generally considered one with such low positive and
negative predictive values that its use should be considered suspect.

ANA tests are limited by the exact opposite problem: they are far too
commonly positive in children to be diagnostically helpful in the
evaluation of common musculoskeletal complaints. Malleson and
colleagues[^10] found that 41% of ANA tests performed at British
Columbia Children's Hospital were positive at titers of 1:20 or greater.
Any test that is positive in 41% of the subjects tested will be
extremely limited as a screening test for relatively rare diseases. Our
group recently attempted to refine the Malleson data by trying to define
settings where the results in ANA testing might be useful,[^11]
specifically asking whether the diagnostic utility of a positive test
improved at higher titers or in specific clinical settings. We found
that ANA titers of children with dermatomyositis, spondyloarthopathy,
and JRA completely overlapped those of healthy children. Thus, as a
screening test for chronic arthritis or inflammatory muscle disease, ANA
tests have absolutely no diagnostic value. Titers of 1:1,080 and higher,
however were commonly seen in children with systemic lupus and rarely
(although occasionally) seen in healthy children. Based on these data,
we recommend that ANA tests be ordered as a screening test in children
to answer only a single diagnostic question: *Does this child have
systemic lupus?* A clinician can feel confident in telling the parent of
a child 10 years of age or younger with an ANA test of [\<]{.underline}
1:160 that, "The ANA test was negative."

In the final analysis pediatric rheumatology remains a "history and
physical" subspecialty. For chronic forms of arthritis, in particular,
there are simply no "tests" that tell a physician that a child has or
doesn't have a given disease. Recognition of chronic forms of arthritis
(and the other rheumatic diseases, for that matter) requires knowledge
of the common presenting symptoms, the age of onset, and the defining
clinical findings. Use of adult models to recognize pediatric diseases
will only be frustrating to the physician and, more importantly,
bothersome (or dangerous) to children and families. All of us start our
pediatrics rotations as third year medical students being told,
"Children are not just small adults." We are still learning that lesson
in pediatric rheumatology.

**References**

1\. Cassidy JT, Athreya B, Pediatric rheumatology: status of the
subspecialty in United States medical schools. *Arthritis Rheum* 1997;
40:1182.

2\. McGhee JL, Burks F, Sheckels J, Jarvis JN, Identifying children with
chronic arthritis based on chief complaints: absence of predictive value
for musculoskeletal pain as an indicator of rheumatic disease in
children. *Pediatrics* 2002; 110: 354-359.

3\. Mauldin J, Cameron D, Jeanotte D, Solomon G, Jarvis JN, Chronic
arthritis in children and adolescents in two Indian Health Service user
populations. BMC Musculoskel Disorders 2004, 5:30.

4\. Schaller JG, Juvenile rheumatoid arthritis: Series 1. *Arthritis
Rheum* 1977; 20 (Suppl):165-170.

5.. Eichenfield AH, Athreya BH, Doughty RA, Cebul RD, Utility of
rheumatoid factor in the diagnosis of juvenile rheumatoid arthritis.
*Pediatr* 1986; 78: 480-484.

6\. Schwarz MM, Simpson P, Kerr KL, Jarvis JN, Juvenile rheumatoid
arthritis in African Americans. *J Rheumatol* 1997; 24: 1826-1829.

7\. Jarvis JN, Cleland SY, Rheumatic disease in Native American
children: opportunities and challenge. *Current Rheumatol Reports* 2003;
5: 471-476.

8\. Agarwal A, Misra R: Juvenile chronic arthritis in India: Is it
different from that seen in Western countries? *Rheum Int* 1994; 14:
53-56.

9\. Malleson PN. Sailer M. Mackinnon MJ. Usefulness of antinuclear
antibody testing to screen for rheumatic diseases. *Arch Dis Child*
1997; 77:299-304.

10\. McGhee JL, Kickingbird L, Jarvis JN, Clinical utility of ANA tests
in children. BMC Pediatrics 2004; 4:13.

**Infectious Disease Updates**.

Rosalyn Singleton, MD, MPH

***Note:** At the 1^st^ International Child Health Meeting in Seattle,
April 2005, several of us met to discuss the disparity in respiratory
hospitalizations among American Indian and Alaska Native (AI/AN)
children. We decided that minimal data were available on viral
etiologies other than RSV. In October 2005 we started the Respiratory
Virus Study with a grant from Medimmune.*

**Study of Virus Etiologies of Respiratory Hospitalizations in Alaska
Native children**

**Background**: Alaska Native infants from the Yukon Kuskokwim Delta
(YKD) of Alaska have some of the highest rates of lower respiratory
tract infection (LRTI) hospitalizations (284/1,000/yr) in the United
States. We conducted active surveillance to describe viral & bacterial
etiologies of LRTI hospitalizations in YK children.

**Methods**: We obtained a nasopharyngeal (NP) swab and NP wash on YKD
children \<3 years of age hospitalized for LRTI. We also collected NP
swabs on healthy children. We performed real time polymerase chain
reaction (PCR) for RSV, influenza A and B, parainfluenza virus (PIV)
1-3, human metapneumovirus (hMPV), rhinovirus, coronavirus (COV) and
pertussis..

**Results**: From Oct. 2005 -- Sept. 2007, we enrolled 434 hospitalized
and 553 healthy children.

**PCR Positives among Cases and Controls**

Oct. 2005 -- Sept. 2007

  -------------------------- ------------------------ --------------------
  Viruses and Pertussis      Hospitalized Cases       Controls

  RSV                        102 (24%)                25 (5%)

  Influenza                  23 (5%)                  11 (2%)

  Parainfluenza              74 (17%)                 23 (4%)

  Metapneumovirus            66 (15%)                 42 (8%)

  Coronavirus                25 (6%)                  29 (5%)

  Rhinovirus                 187 (43%)                176 (32%)

  Pertussis                  7 (2%)                   0 (0)
  -------------------------- ------------------------ --------------------

\*Excluding rhinovirus 41 (9%) of the positive cases were co-infected
with 2 or more viruses.

**Highlights**:

1\. RSV was the most common virus, but we found an unusually high
proportion of hMPV.

2\. Rhinovirus occurred in nearly half of cases but was also common
among controls that may have had minor cold symptoms.

3\. Pertussis only occurred during a known outbreak; however, we
identified 5 hospitalized children with pertussis who were not
clinically recognized.

4\. Peak RSV and PIV activity occurred 2-3 months after the U.S. peak
activity.

*Study institutions:* Alaska Native Tribal Health Consortium; Arctic
Investigations Program-CDC; Yukon Kuskokwim Health Corporation; U of
Washington; CDC/CCID Atlanta, GA.

**Recent literature on American Indian/Alaskan Native Health**

Doug Esposito, MD

**[Article]{.underline}**

**[Article]{.underline}**

[Tsosie
R.](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17714250&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Cultural challenges to biotechnology: Native American genetic resources
and the concept of cultural harm*. J Law Med Ethics*. 2007
Sep;35(3):396-411.
<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17714250&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum>

**Summary**

This article explores the issue of rights to ownership and privacy of
human tissue and the knowledge and products derived from the study of
that tissue. Anglo-American legal doctrine essentially approaches the
resolution of conflicts in this arena from a personal property and
privacy perspective; rights which are fundamentally protected by the
U.S. Constitution. From a Western cultural standpoint, although not
perfect, this doctrine seems to function reasonably well for settling
conflicts arising from issues of ownership and use/misuse of information
in biotechnology for members of the dominant culture. However, the
author of this article suggests that "the interests of Native groups
cannot be accurately understood or assessed within our legal system
unless we attempt to understand the different normative conceptions of
property, ownership, and privacy that exist for these groups," and that
"claims made by an individual or group that are perceived to be
asserting a cultural or spiritual harm based on the alleged misuse or
mishandling of blood, tissue, or knowledge gained from DNA analysis may
not be cognizable within existing legal theories." As a function of
these and related concerns and histories, indigenous individuals and
groups are legitimately suspicious of medical research and
biotechnology. Deriving from the concept of "cultural rights" as applied
in international human rights law, the creation of legal protection
based upon "cultural harm" is offered as a possible solution to these
issues for Native people.

**Editorial Comment**

I must admit that I have at best a rudimentary fluency in legal language
and thought. As a result, I am certain that many of the points made in
this article passed over my head at least at the 10,000 foot level!
Nevertheless, the conceptual framework presented by the author was very
useful in helping me to develop a deeper understanding of the concerns
and suspicions that Native individuals and groups have with respect to
biotechnology and medical research. I have been cognizant of these
issues for quite some time but have never really had a complete grasp of
the complexity of the concerns. For anyone desiring a better
understanding of the potential dangers that biotechnological advances
and medical research pose to underrepresented indigenous individuals and
populations, I would certainly recommend taking a look at this article.
It is well worth the difficulty of delving into the unfamiliar (and
uncomfortable) realm of legalese.

**Additional Reading**

Pevar, S.L. (2004): *The Rights of Indians and Tribes: The Authoritative
ACLU Guide to Indian and Tribal Rights*. 3^rd^ Ed. New York, New York
University Press.

<http://www.amazon.ca/Rights-Indians-Tribes-Authoritative-Indian/dp/0814767184/ref=sr_1_3/702-4509498-9742412?ie=UTF8&s=books&qid=1191619654&sr=1-3>

**[Article]{.underline}**

[Singh GK, Kogan
MD.](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17666705&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Widening socioeconomic disparities in US childhood mortality, 1969-2000.
*Am J Public Health*. 2007 Sep;97(9):1658-65.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17666705&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum>

**Editorial Comment**

The authors investigate the impact of socioeconomic disadvantage on
trends in childhood mortality over a 30 year period. Although
socioeconomic status (SES) is a well accepted modulator of childhood
mortality, with lower standing having been shown to be inversely related
to mortality in a number of studies, the authors claim that theirs is
the first study linking measures of poverty to longitudinal trends in
mortality. A description of the methods by which this is achieved and a
repeat of all of the fascinating results and conclusions is beyond the
scope of this review. I would encourage you all to check out this
excellent report for yourselves. It really is timely and relevant!

On a positive note, overall mortality rates for children have been
declining over the past three decades. However, the speed of this
decline has not been equal for all racial/ethnic groups or socioeconomic
strata within our society. As we have observed from childhood injury
mortality data recently reviewed in the *IHS Child Health Notes*,^1,2^
mortality rates for minorities and those standing on the lower rungs of
the socioeconomic ladder relative to white, less deprived groups are
RISING in the U.S. That is, disparities are increasing rather than
decreasing, rendering Goal 2 of *Healthy People 2010* (the
[elimination]{.underline} of health disparities by the year 2010) all
but an optimist's fantasy at this point. This paper goes on to suggest
that this deterioration in relative mortality appears to be associated
with longitudinally increasing inequity in SES within and between
certain groups and regions in the U.S., even as the overall economy has
improved. A sadder reality could not exist! As the wealthiest and most
powerful nation on earth, can't we expect better?

The authors state that, "compared with children in the least deprived
socioeconomic quintile, the mortality rate for children in the most
deprived socioeconomic quintile was 52% higher in 1969--1971, 65% higher
in 1988--1990, and 86% higher in 1998--2000." Furthermore, due to
technical and methodological issues and dilutional effects of SES in the
sampling units, these differences likely represent an underestimate of
the true mortality, and by extension, disparity. And, this is not to
mention the sizable impact that racial misclassification has on
underestimating mortality rates for AIAN minorities in studies dependent
on data from the National Vital Statistics System.^1,2^

So, as time runs out on *Healthy People 2010* and ever increasing and
thoughtful data emerges demonstrating persistent and widening health
disparities, I cannot help but wonder: will we redouble our efforts and
target their elimination for the year 2020, or will we move on to
something new? Sorry for the sarcasm, but I just don't understand why we
can't seem to get it right!

**References**

1\. Holve, S.A. ed. (2007 June/July). *IHS Child Health Notes*.

<http://www.ihs.gov/MedicalPrograms/MCH/M/documents/IHSchildnotesJune2007.doc>

2\. Holve, S.A. ed. (2007 August). *IHS Child Health Notes*.

<http://www.ihs.gov/MedicalPrograms/MCH/M/documents/ICHN807.doc>

[^1]: James N. Jarvis, M.D., Basic Sciences Education Bldg, BSEB #235A,
    Oklahoma City, OK 73104.

    E-mail: james-jarvis@ouhsc.edu

[^2]: Cassidy JT, Athreya B, Pediatric rheumatology: status of the
    subspecialty in United States medical schools. *Arthritis Rheum*
    1997; 40:1182.

[^3]: McGhee JL, Burks F, Sheckels J, Jarvis JN, Identifying children
    with chronic arthritis based on chief complaints: absence of
    predictive value for musculoskeletal pain as an indicator of
    rheumatic disease in children. *Pediatrics* 2002; 110: 354-359.

[^4]: Mauldin J, Cameron D, Jeanotte D, Solomon G, Jarvis JN, Chronic
    arthritis in children and adolescents in two Indian Health Service
    user populations. BMC Musculoskel Disorders 2004, 5:30.

[^5]: Schaller JG, Juvenile rheumatoid arthritis: Series 1. *Arthritis
    Rheum* 1977; 20 (Suppl):165-170.

[^6]: Eichenfield AH, Athreya BH, Doughty RA, Cebul RD, Utility of
    rheumatoid factor in the diagnosis of juvenile rheumatoid arthritis.
    *Pediatr* 1986; 78: 480-484.

[^7]: Schwarz MM, Simpson P, Kerr KL, Jarvis JN, Juvenile rheumatoid
    arthritis in African Americans. *J Rheumatol* 1997; 24: 1826-1829.

[^8]: Jarvis JN, Cleland SY, Rheumatic disease in Native American
    children: opportunities and challenge. *Current Rheumatol Reports*
    2003; 5: 471-476.

[^9]: Agarwal A, Misra R: Juvenile chronic arthritis in India: Is it
    different from that seen in Western countries? *Rheum Int* 1994; 14:
    53-56.

[^10]: Malleson PN. Sailer M. Mackinnon MJ. Usefulness of antinuclear
    antibody testing to screen for rheumatic diseases. *Arch Dis Child*
    1997; 77:299-304.

[^11]: ^?^ McGhee JL, Kickingbird L, Jarvis JN, Clinical utility of ANA
    tests in children. BMC Pediatrics 2004; 4:13.