Word count: 3484

Jatan Kothari

Abstract
15 year old male presenting with Henoch-Schnlein Purpura. Associated
symptoms are indicative of HSP without progression onto HSP Nephritis. This
case report discusses the presentation of typical symptoms found in HSP
sufferers and explains the epidemiology, pathophysiology and treatment of
the disease as well as dental implications of HSP.

Case report

Presenting complaint:
Male child 15y/o presents in A&E with worsening abdominal pains last 2
days (26th November 2015).
Vomited 8 times overnight - dark green and bilious.
Unable to tolerate fluids or food.
Pt unable to open bowels for last 2 days.
Temperature 36.4C
Glasgow Coma Scale 15.
Urine dip NAD
Examination:
o Cardiovascular:
Pulse elevated at 132bpm (tachycardia) Increased values
Blood Pressure elevated at 139/96 most likely due to
o Respiratory: pain and stress
Respiratory rate elevated at 20 per minute
o Abdomen: Soft on palpitation, pain generalised over majority of
stomach area
o Musculoskeletal NAD
o Neurological NAD

History of Presenting Complaint:

Diagnosed with Henoch-Schnlein Purpura in mid-October by GP.
Second admission to A&E in last 2 weeks for increasing abdominal pain
with constipation and vomiting
Presented with rash around ankle and back of calf which subsequently
scarred and blistered. A week after the first rash appeared, mild
stomach cramps began which came and went.
Rash spread upwards to cover whole of legs, arms and genitalia.
Rashes don't disappear; they flare up and return to original appearance
appearance resembles acne.
Constant stomach pain across whole stomach area. Pain presented in
waves rating from 3/10 to 7/10
Pain killers (Paracetamol, ibuprofen) haven't helped.
Hot water bottle helped.
Stools are now runny
Joints have been aching; presents with swollen left wrist and both
 ankles.
Has also been feeling light-headed, and been extremely tired.
Medical History:
No other relevant medication conditions or ailments
No allergies

Social History:
Lives with parents and brother
Non drinker
Non smoker
Student in school

Family History:
N/A

Medication History:

Name Dose Frequency Reason

Prednisalone 10mg Once per day Prescribed by GP after
taken orally diagnosing HSP To
1g Intravenous controls/prevents
Methylprednisal pulse therapy inflammation
one for 3 days IV dose administered after
second visit to A&E due to
continued symptoms
(Emedicine.medscape.com,
2015)
Paracetamol 1g Intravenous Prescribed after 2nd A&E
administration admission - To relieve pain
for 3 days
Ibuprofen 400mg Taken orally 3 Given at 2nd A&E admission
times a day - Inhibits inflammatory
reactions and pain
Movicol 13.8g (one 2-3 sachets Given at 1st A&E admission
sachet) daily as and dose increased after
needed 2nd - Prescribed to relieve
constipation,
Bucospan 10mg Intravenous Given at 2nd A&E admission
administration To relieve GI spasm
related pain
Cyclozine 50mg Intravenous Given at 2nd A&E admission
administration Antihistamine to reduce
 vomiting and nausea

Special Investigations:

X-ray: Shows stool present in bowels

Abdominal Ultrasound: Shows intermittent intussusception in ileo-colic

region and localised thickening of bowel walls

Blood sample and full count

Patient PH 7.43 MCH 31.4 pg/L

sample pCO2 5.0 kPa RDW 13.3 %
report pO2 10.9 kPa NEUT 14.3
109/L*
Na 133 NEUT 85 %
mmol/L
K 4.9 mmol/L Lymph 1.7 109/L
Cl 102 Lymph 10 %
mmol/L
Ca 1.22 Mono 0.7 109/L
mmol/L
Glucose 6.1 mmol/L Mono 4%
Lactose 2.0 mmol/L EOS 0.1 109/L
Renal Serum 139 EOS 1%
Profile sodium mmol/L
Serum 4.1 mmol/L BASO 0.1 109/L
Potassium
Serum 67 mmol/L BASO 0%
Creatinine
Serum 4.1 mmol/L INR 1.0
Urea
Glucose Plasma 5.0 mmol/L PT 12.3 s
plasma glucose
C-reactive Serum CRP 1.1 mg/L Fibrinogen 3.6g/L
protein derived
Liver Serum 13 umol/L Co- Hb 157 %
profile bilirubin oximetry
ALT 12 umol/L O2Hb 95.7 %
ALK 132 u/L COHb 2.2 %
Phosphatas
e
 Albumin 40 g/L MetHB 1.0 %
Full blood HB 146 g/L HHb 1.2 %
count WBC 16.9 sO2 98.8 %
109/L*
PLTS 374 109/L Derived TCO2 28.0
mmol/L
RCC 5.06 109/L BE(B) 3.3mmol/L
HCT 0.425 109/L HCO3- 26.9
mmol/L
MCV 84 fl HCO3- 27.4
(std) mmol/L
MCH 28.9 pg HCT 47%

*results outside the normal considered range

Discussion

Henoch-Schonlein Purpura (HSP) is vasculitis of the small vessels, and is the

most common vasculitis of childhood. (Roberts 2007) More than 90% of HSP
patients are under 10 years of age with differences across incidence figures
across various ethnicities being observed: Asian 20.4, Caucasian 17.8 and
Afro-Caribbean 6.2 per 100,000. (He 2013)

HSP is most commonly characterised by non-thrombocytopenic palpable

purpura, abdominal pain, arthritis, gastrointestinal bleeding and
glomerulonephritis. (Roberts 2007) Due to the varied nature of the
symptoms across several body systems, either one of the presentations
could point to a differential diagnosis. These can include: acute
glomerulonephritis, inflammatory bowel disease, IgA nephropathy,
Kawasakis disease or Intussusception. (Emedicine.medscape.com 2015).
These are but a few of the possible conditions that can be explained by the
symptoms individually, but the presentation of several of these symptoms
alongside an accurate history and the presentation of widespread rashes
over the lower limbs help point to HSP.

The causes of HSP at this time cannot be confirmed but a number of theories
and indications have been proposed. The vascular and renal mesangium
deposition of IgA-dominant immune complex, infiltration of small blood
vessels with polymorphonuclear leukocytes, and the presence of
leukocteoclasia, increased serum IgA and proinflammatory cytokines suggest
that HSP is an immune-mediated disease. (He 2013) This is observed in the
case-patient through an increased level of neutrophils in the blood.

IgA has two subclasses: IgA1 and IgA2 but only IgA1 is involved in the
pathogenesis of HSP. This is possibly due to the aberrant glycolysation of O-
linked glycolysation sites found in the hinge region in IgA1 (a region not
found in the IgA2 subclass). The mechanism of the glycolysation defects of
IgA1 in patients with HSP is unclear; without enough research into whether
these defects continue following resolution of clinical symptoms, we are
unable to ascertain whether this glycolysation is due to genetic factors or
simply a consequence of the disease itself. (He 2013)

Studies show that genetic variants in HLA, class II antigens, RAS and MEFV
may confer susceptibility for HSP. (He 2013) In particular there is a
prevalence of mutations in the MEFV gene in patients with Familial
Mediterranean Fever (FMF) - a genetically determined autoinflammatory
disease that presents with HSP - than in those without the disease. However,
the broader implications of this finding would not extend to countries where
FMF is not common so cannot be relied on as a genetic basis of the disease.
(Saulsbury 2010) Since the case-patient is of British heritage it is unlikely
that his symptoms are as a result of FMF.

HSP is frequently reported to follow respiratory tract infections; therefore

various viral and bacterial pathogens have been implicated as triggers of the
disease. Deposits of IgA-binding streptococcal M protein in the renal
mesangium and skin vessels have been found in some patients with HSP;
further research using a larger study sample would help to ascertain the link
between streptococcal infection and the development of HSP in some
patients. (Saulsbury 2010) Interestingly the case-patient reported that a
week before the first of the rashes developed he had seen a GP due to ill
health; which was diagnosed at the time as a cold. Other potential reasons
for the development of HSP include food and drug allergies/reactions, insect
bites and exposure to cold. (Al-Sheyyab M, 1999)

In all clinical cases of HSP the patient will develop a rash. (Roberts, P 2007)
For the case-patient the rash began on the ankles and calf. These rashes
were larger, bullous and painful in comparison to the subsequent rashes on
the rest of the body - which followed the more conventional characteristic of
red/brown, non-blanching, palpable 5-10mm in diameter purpura that spread
up the entire leg, arm and genitalia a week after the initial symptoms and
ankle rash appeared. These rashes represent extravasation of blood into the
skin and although the reasoning for this has yet to be ascertain it is most
likely to be due to increased permeability and pressure found in the blood
vessels in these limbs. The case-patient described the rashes as "coming and
going" but never fading away and this cycle would take roughly two weeks
(Lui 2015). Unusually, the original rash blistered four weeks after initial
presentation; the reason for this is unknown.

Polyarthralgia is present in 80% of patients and is most commonly found in

the knees and ankles and is associated with oedema. (Roberts 2007) This
presented in the case-patient as aching joints in his ankles as well as his left
wrist which faded away after a few days each time it appeared. Local
swelling was also found the in testicles of the patient with tenderness on
touch. This is a more rare manifestation of HSP but has been found in a
significant number of cases however it is often misdiagnosed or unreported.
(Dalpiaz 2015) The link between HSP and testicular inflammation is unclear
but like the polyarthralgia of his ankles and wrists, it returned back to normal
a few days after symptoms began.

Gastrointestinal symptoms are the next most common and are found in 50-
65% of patients. Oedema and palpable purpura above the waist was
significantly associated with patients who presented with gastrointestinal
involvement, as seen in the case-patient. (Hoeger 2015) Abdominal pain
usually develops 8 days after the initial rash and is generally associated with
nausea, vomiting, diarrhoea or constipation. (Roberts 2007) The pain is
characteristically colicky and localised to the periumbilical and epigastric
regions and it worsens after meals - similar to bowel angina or ischemia.
(Ebert 2008) For the case-patient, the abdominal pain began as mild
stomach cramps which progressed to fairly severe pain that presented in
"waves" and ranged from a 3/10 pain score to 7/10; it was clinically identified
by a generalised tenderness on palpation alongside guarding by the patient.
In addition the patient presented with nausea, vomiting and constipation.
The vomit was especially of notice as it presented as dark green and bilious.
Bile in vomit is frequently associated with an obstruction of the small
intestine as far as the jejunum or the ileum. The constipation and green,
bilious vomit meant an x-ray and ultrasound of the region was required. The
x-ray showed stool present in the bowels and the ultrasound showed
intermittent intussusception and bowel wall thickening. The GI tract is
generally free of damage by the vasculitis in medium-sized vessels due to its
redundant circulation however the small intestinal villi contains loops of
vessels with end-capillaries that, when obstructed, result in necrosis of the
villus tip. In the case-patient, intermittent intussusception was found in the
ileo-colic region, an area where 39% of intussusceptions occurs and 80-90%
if cause is idiopathic. The intermittent nature of it negates surgical
intervention at this stage and may require an air or barium enema to clear; if
in 24hours this is subsequently not cleared, then a surgical intervention may
be indicated. (Ebert 2008)

HSP is generally considered to be a self-limiting condition but 30-50% of

patients can develop HSP Nephritis (HSPN) within 4 to 6 weeks of initial
presentation. The majority of these patients will have a mild form of the
disease, presenting with haematuria and/or low grade proteinuria with a
good chance of recovery. But in 20% (7% of all HSP sufferers) this can
develop into renal function impairment or nephrotic syndrome and 1-7% may
progress to renal failure or end-stage renal disease. (Chen 2014) In patients
with HSPN, enzymes that interact with the hinge region on IgA1 molecules
are reduced and this in turn leads to the aberrantly glycolsylated IgA1
molecules forming immune complexes with IgG antibodies specific to these
galactose-deficient IgA1 molecules. The inhibition of the binding of IgA
molecules to hepatic receptors and their formation increases the amount of
IgA immune complexes in circulation. These molecules deposit themselves in
the renal mesangial areas and activate the complement system, as well as
playing a role in mesangial cell proliferation, matrix expansion and
inflammatory cell recruitment. (Chen 2014) Usual clinical manifestations of
HSP progressing onto HSPN include haematuria and proteinuria and are
tested with a urine dip test, which for the case-patient came back as
negative both times he was admitted to A&E. Although this does not
conclusively suggest that he will not develop an impaired renal function, the
information at this current point in time and lack of nephrotic involvement at
this stage 6 weeks after initial diagnosis suggests that it is unlikely to occur
at this point.

Diagnosis

The patient was diagnosed with HSP by his GP in mid-October; the diagnosis
follows the 2006 classification of HSP by the European League against
Rheumatism and Paediatric Rheumatology European Society:

Palpable purpura in presence of any of the following

o Diffuse abdominal pain
o Any biopsy showing predominant IgA
o Acute arthritis/arthralgia
o Renal involvement defined as any haematuria or proteinuria
(McCarthy 2009)

Treatment

The goal of treating HSP would be to 1) Ameliorate acute symptoms, 2)

Mitigate short term morbidity and 3) prevent chronic renal insufficiency. The
patient was prescribed 10mg oral Prednisolone to combat these symptoms;
Prednisolone is a glucocorticoid which is used to inhibit inflammatory
processes; early administration is said to attempt to achieve these goals
albeit with some controversy surrounding them. In a systematic review,
glucocorticoids were tested to see if early intervention aided in the treatment
or resolution of the symptoms or further pathology. Although the review
states the need for a more complete understanding of how corticosteroids
impact HSP, it found across the whole analysis the pattern favoured the use
with none indicating any harm. Glucocorticoid treatment did not reduce the
median time to resolution of abdominal pain but did significantly reduce the
mean resolution time and increased the odds of resolution within 24 hours.
The review states that early corticosteroid treatment did significantly reduce
the odds of developing persistent renal disease however this is the area of
biggest controversy. (Weiss 2007) One of the randomised controlled trials
stated in the review states that there is no statistically significant difference
between prednisone and a placebo in the progression to renal involvement
within the year (3/21 in the trial group and 2/19 in the placebo group);
although the research sample is small, it may suggest a larger randomised
controlled trial is still needed in order to determine what the best course of
action is to prevent renal involvement. (Huber 2004)

Glucocorticoids have many serious side effects which are important to

consider. The case-patient had been prescribed 10mg Oral Prednisolone from
mid-October onwards and soon after his second visit to A&E was started on a
3-day course of 1mg Methylprednisalone pulse therapy. As treatment has
gone on for six weeks the patient must be weaned off the drug following the
resolution of symptoms in order to avoid any adrenal insufficiency. As a result
of treatment, the patient also reported that he was feeling lightheaded, had
trouble eating and felt extreme tiredness. Furthermore, both he and his
parents reported that he was feeling depressed and constantly irritated - all
commonly reported side effects of systemic steroid treatments. The effects
of this on the patient cannot be understated; the patient has been unable to
attend school for over 6 weeks and in addition the patient has a professional
rugby contract and would have put him out of action for key moments during
the current rugby season and is unlikely to play until sometime in early 2016.
Socially, the main impact of hospitalisation is isolation which can only
negatively affect the patients psychological and mental state. The
widespread rashes are incredibly noticeable and for an adolescent in school
is likely to be a source of ostracization and ridicule which may further
negatively impact the mental state of the patient and lead to feelings of
stress, anxiety, anger, depression, shame, low self-esteem and
embarrassment. The resolution of this would only come at a point when all of
his symptoms have been alleviated and he is able to return to school;
however even this would be a source of short term stress as its commonly
found amongst students returning to school after a long-stay in hospital for
individuals for their peer group to treat them with a certain amount of
wariness due to a lack of understanding over what the condition was and
how especially it is unlikely to be infectious. (All Party Parliamentary Group
on Skin 2013)

Dental implications

A low mood and extreme lack of energy would normally have an overall
impact on the case-patients ability to take care of themselves. In this
instance the patient is 15 so at home his care is supervised by his parents
and once in hospital is supervised by the medical staff. However, it is
important to mention that his dental health has clearly suffered throughout
the course of his ailment. The case-patient reports that he lacks the energy
to brush on his own and in the last 6 weeks his oral health has been severely
lacking through not brushing on consecutive days and most importantly not
frequently brushing at night: 3-4 days per week. The case-patients extreme
tiredness also means he takes frequent naps during the day, increasing the
number of times salivary flow is reduced and demineralisation of enamel can
occur through poor plaque control and acidic attack by oral bacteria.

The medication prescribed to the patient can further the negative impact on
the case-patients plaque control. The case-patient has reported to have felt
his mouth to be dryer than usual and lips constantly chapped; in addition has
reported that his tongue felt like it was cracking and on presentation
appeared white and scaly. All of these are indications that the patient has low
salivary flow and is possibly dehydrated. These can be explained by the
prescription of Movicol given to the patient following his first admittance to
A&E when presenting with constipation. The use of Macrogol osmotic
laxatives leads to diarrhoea which is associated with subsequent
dehydration; the patient would need to consume more water in order to
combat these symptoms.

The above will all lead to poor plaque control and increased demineralisation
of the patients enamel, which if continued can lead to decreasing gingival
health and an increased chance of infection of the tooth and root system.
However, the dental implications of HSP are far more encompassing than
symptom/medication related by-products of the disease. In a case-study of a
14 year old patient receiving endodontic treatment, the appearance of a
macular rash evolving into purpuric lesions occurred within a few days of
obturation of her UL1 the paediatrician confirmed therefore the aetiological
trigger was either the root canal therapy or the long standing dentoalveolar
lesion. (Tahmassebi 2007) This is not an isolated case and may further
support the claim that HSP stems from an upper respiratory tract infection.

To further this claim, a study in the efficacy of early dental and ENT therapy
to prevent nephropathy in paediatric HSP patients had been carried out. The
focal point of infection was first identified in 40 newly diagnosed HSP
patients. In 70% (28/40) of patients, dental caries was the focal point of
infection and in 53% (21/40) apical periodontitis was identified. Other
sources of infection were rhinosinusitis, tonsillitis and otitis media and for
43% of patients, there were two simultaneously occurring focal points all
patients presenting with apical periodontitis had dental caries as their other
focal infection point. Dental caries was measured with dmft scores of
5.04.3 and apical periodontitis noted by the presence of apical radiolucency
on a radiograph.

The result of dental and/or ENT therapy alongside antibiotics resulted in the
complete cure without development of HSPN or recurrent attacks in 80%
(32/40) of patients. The study was carried out after a previous study by the
same team where tonsillectomy demonstrated the early recovery from
proteinuric HSPN, shortening the disease duration until urinalysis returned to
normal. The study suggested tonsils may be involved in the pathogenesis of
HSPN and since the oral and sinonasal cavities are anatomically directly
connected to the tonsils, it was theorised that these may be potential
infection points leading to infection of the tonsils and subsequently HSP with
potential further pathology.

The treatment specifically for the patients with dental caries and apical
periodontitis was removal of any tooth showing signs of abscess (parulis,
fistulous tract or bony expansion), pulpotomy/pulpectomy of the remaining
patients and increased diet and hygiene advice for the parents of all dentally
affected patients. (Inoue 2008) The oral implications for HSP are therefore
somewhat substantial, and the aetiological role is supported by the presence
of antigens of Haemophilus Parainfluenzae a common bacterium found in
apical periodontitis and antibodies against these being identified in the
glomerular mesangium and sera of HSP and IgA nephropathy patients. Apical
periodontitis associated with dental caries is therefore implicated as the
most obvious oral focal point of infection in HSP patients. The disease which
is mostly initiated by dental caries by bacteria invading through infected root
canals is a complex disorder with more than 300 species of aerobic and
anaerobic bacteria being isolated from lesions. Associated with this, various
inflammatory cytokines are produced leading to the persistence of active
immune reactions. The bacteria and their toxic derivatives may continue
onto the tonsils through their surface epithelium or may enter the blood
stream during transient bacteraemia, damaging the smooth lining of blood
vessel walls. Collectively considering both standpoints, its clear that chronic
and long-standing apical periodontitis have the potential to trigger HSP.
(Pertiwi 2012)

The case-patient has not had any dental related pain in the last 2 years and
is reported to have had an adequate oral health with limited past dental
experience - only extractions for orthodontic treatment. It would be unwise
from this analysis to suggest oral disease as a trigger for HSP but the lack of
adequate plaque control is important to bear in mind as it can lead to future
infection of the oral cavity which has the potential to trigger HSP.

Conclusion

HSP is the most common form of vasculitis found in child patients and its
symptoms affect various body systems to varying degrees. It is the observed
symptoms identified in groups alongside the characteristic rashes that allow
for differentiation from other diagnosis. Early systemic corticosteroid
treatment should commence on initial diagnosis which should reduce the
length of time symptoms occur; but it does not reduce severity of symptoms
and there is a lack of evidence on whether they better prognosis from
nephritis. Oral health can be affected by the course of treatment especially if
the symptoms include constipation for which a laxative must be used from
dehydration. However an increase in the promotion of oral health can be
seen to reduce the incidence of HSP as dental caries and apical periodontitis
are seen to be focal infection points that can trigger the disease and their
removal can help in the therapy of those who contract it. For the case-
patient; at 6 weeks from the initial diagnosis and commencement of
systemic steroids the symptoms have lasted longer than usual but the lack
of nephrotic involvement at this stage does decrease the likelihood of renal
issues pointing to a more favourable diagnosis.
Bibliography:

Al-Sheyyab M, Batieha A, el-Shanti H, Daoud A.HenochSchnlein purpura

and streptococcal infection:a prospective case control study.Ann Trop
Paediatr1999;19: 253255.
All Party Parliamentary Group on Skin, (2013). The psychological and social
impact of skin diseases on peoples lives. London: All Party Parliamentary
Group on Skin.

Chen, J. and Mao, J. (2014). Henoch-Schnlein purpura nephritis in children:

incidence, pathogenesis and management. World Journal of Pediatrics,
11(1), pp.29-34.

Lui. L-J, Yu J, Li Y-N. (2015) Clinical characteristics of Henoch-Schnlein

purpura in children. Chin J Contemp Pediatr, 17(10), pp.1079-1083.

Dalpiaz, A., Schwamb, R., Miao, Y., Gonka, J., Walzter, W. and Khan, S. (2015).
Urological Manifestations of Henoch-Schonlein Purpura: A
Review. Current Urology, 8(2), pp.66-73.

Ebert, E. (2008). Gastrointestinal Manifestations of Henoch-Schonlein

Purpura. Dig Dis Sci, 53(8), pp.2011-2019.

Emedicine.medscape.com, (2015). Henoch-Schonlein Purpura: Practice

Essentials, Background, Pathophysiology. [online] Available at:
http://emedicine.medscape.com/article/984105-overview [Accessed 12
Dec. 2015].

Emedicine.medscape.com, (2015). Henoch-Schonlein Purpura Medication:

Immunosuppressants, Analgesic Agents. [online] Available at:
http://emedicine.medscape.com/article/984105-medication [Accessed 12
Dec. 2015].
He, X., Yu, C., Zhao, P., Ding, Y., Liang, X., Zhao, Y., Yue, X., Wu, Y. and Yin, W.
(2013). The genetics of HenochSchnlein purpura: a systematic review
and meta-analysis. Rheumatol Int, 33(6), pp.1387-1395.

Pertiwi, A (2012) Henoch-Schnlein purpura in children: its relation to oral

and general health. Dental journal, 45(3), pp.127-132.

Hoeger, P. (2015). Prognostic parameters in Henoch-Schnlein purpura. Br J

Dermatol, 172(5), pp.1191-1192.

Huber, A et al (2004). A randomized. placebo-controlled trial of prednisone in

early Henoch Schnlein purpura. BMC Med 2004., 2(7).

Inoue, C., Nagasaka, T., Matsutani, S., Ishidoya, M., Homma, R. and Chiba, Y.
(2008). Efficacy of early dental and ENT therapy in preventing
nephropathy in pediatric Henoch-Schnlein purpura.Clin Rheumatol,
27(12), pp.1489-1496.

McCarthy, H. and Tizard, E. (2009). Clinical practice:. European Journal of

Pediatrics, 169(6), pp.643-650.

Roberts, P., Waller, T., Brinker, T., Riffe, I., Sayre, J. and Bratton, R. (2007).
Henoch-Schnlein Purpura: A Review Article. Southern Medical Journal,
100(8), pp.821-824.

Saulsbury, F. (2010). HenochSchnlein purpura. Current Opinion in

Rheumatology, 22(5), pp.598-602.

Tahmassebi, J. and Paterson, S. (2007). Development of acute Henoch

Schonlein purpura subsequent to endodontic treatment. International
Journal of Paediatric Dentistry, 17(3), pp.217-222.

Weiss, P., Feinstein, J., Luan, X., Burnham, J. and Feudtner, C. (2007). Effects
of Corticosteroid on Henoch-Schonlein Purpura: A Systematic
Review. PEDIATRICS, 120(5), pp.1079-1087.