ABAD.IMPERIAL.JAVATE. PALMA.UY, R. VALENCIA A Curious Case of Rashes

General Data Name:N. E. Age:9 Gender:F Nationality:Filipino Civil Status: Single Religion:Roman Catholic Occupation:Student Address:Antipolo, Rizal Informant: Patient and parents Reliability:Good

Chief Complaint Abdominal Pain

History of Present Illness 2 Weeks Prior to Admission  Fever that spontaneously resolved with paracetamol 4 Days Prior to Admission  Productive cough  Sought consult and was prescribed Amoxicillin  Developed non-pruritic rashes on her anklesthat night  Mother gave antihistamines which reduced the redness but not the number 3 Days Prior to Admission  Noted increase in number of rashes

History of Present Illness 2 Days Prior to Admission  mother noted that the patient was complaining of pain on her left ankle  Consulted a “hilot” which supposedly afforded partial relief 1 Day Prior to Admission  One episode of vomiting, followed by generalized abdominal pain described as crampy, waxing, and waning  Sought consult CBC showed normal findings Prescribed Maalox A few hours Prior to Admission  Abdominal pain became more severe (10/10);  No vomitting or diarrhea

Diagnostic Plan Date HgbHct WBC NLME PLT June June

Other Pertinent Findings Review of Systems  On and Off cough Past Medical History  No previous hospitalizations Immunization History  Had: BCG, DPT/Polio (1-2-3 booster 1-2), Hep B (1-2-3), MMR (1-2), Measles (1) Varicella (1)  Did not have: Pneumococcal, Influenza, Rotavirus, Hep A, Typhoid  Unknown: HiB

HEADSSS Home  Patient lives with the parents. Has an older sibling (Grade 7). Gets along well with family members Education  Incoming Grade 4 student in LaSalle Antipolo Activity  Doesn’t go outside to play. Stays at home and plays computer games most of the time Drugs, Sexual Activity, Substance Abuse  not asked Safety  Patient feels safe at home and doesn’t perceive any threat to her well being

Physical Examination Vital Signs  T 37.1 HR 84 bpm PR 19 bpm BP 100/70 W 25.7 kg H 134 cm  Height for age: 25 th -50 th Percentile  Weight for age: 10 th Percentile  BMI for age: 9 th Percentile General Appearance  Pale and ill-looking

Physical Examination Skin  Multiple violaeceous, palpable, non-blanching, purpuric rash from ankles to knees Abdomen  Generalized tenderness on deep palpation of abdomen  Soft abdomen  No masses  No rebound tenderness  No guarding

PE Findings HEENT  Anicteric Sclerae, Pink Palpebral Conjunctivae  (-) TPC, (-) CLAD, Non-distended neck veins Pulmonary  Clear breath sounds, no rales or wheezes Cardiovascular  Normal rate, regular rhythm, no murmurs Extremities  Full and equal pulses, pink skin color, good turgor, no edema, no cyanosis Neurological Exam  Alert and coherent, intact cranial nerves, good muscle tone

Initial Plan T/c Henoch Schonlein Purpura Admit to ward for further assessment and management

PROGRESS NOTES LAB RESULTS Course in the Ward

SUBJECTIVEOBJECTIVEASSESSMENTPLAN Generalized crampy and waning abdominal pain (10/10) rashes on lower extremities HR 80 RR 20 BP 90/60 Temp 36.4 ∘ UO: 0.36 ml/kg soft abdomen, no masses (+) direct tenderness in LLQ, epigastric, and LUQ (-) rebound tenderness (-) guarding (+) pinpoint, erythematous papular rash on both arms and legs, non-blanching and non-pruritic t/c Henoch Schonlein Purpura nonsurgical abdomen strict I and O monitor BP suggest Prednisone Day 1 (*Consult with Surgery)

Labs Day 1 Urinalysis

Labs Day 1 Urinalysis

Labs Day 1 Blood Chemistry  CrCl – Schwartz 150 mL/min/173m 2  Counahan Baratt 118 mL/min/173m 2  BUN-Creatinine ratio - 19 ESR  23 (0-20)

DifferentialsRule InRule Out Henoch-Schönlein PurpuraThe American College of Rheumatology 1990 criteria for the classification of HSP aimed to identify diagnostic criteria to differentiate HSP from other vasculitic diseases: The four criteria identified, of which two are necessary to make the diagnosis, are:  age < 20 years at onset  palpable purpura  “bowel angina” (diffuse or colicky abdominal pain or bowel ischaemia usually with bloody diarrhoea)  biopsy evidence of granulocytes in the walls of arterioles or venules Hallmark of the disease: pinkish maculopapular rash that turns into a palpable purpura and petechiae Presence of joint pain in the ankle

DifferentialsRule InRule Out Systemic Lupus Erythematosus The triad of fever, joint pain, and rash in the patient suggests the diagnosis of systemic lupus erythematosus (SLE). These three symptoms are the usual or common manifestations of patients with SLE. However, a person can be diagnosed with SLE if any 4 or more of the 11 criteria of the diagnostic criteria for SLE are present, serially or simultaneously, during any interval of observation. - American College of Rheumatology Wegener’s granulomatosis Presence of nonspecific constitutional symptoms such as fever and arthralgia Cutaneous lesions include palpable purpura and cough may be a symptom present later on The frequency of different system involvement is respiratory tract in 87% of cases, kidneys in 53%, joints in 53%, eyes in 53%, skin in 53%, sinuses 35%, and nervous system in 12%. Systemic- onset Juvenile Rheumatoid Arthritis Joint pain and rashHowever, it does not explain the fever and the abdominal pain. It does not follow the Criteria for the Classification of Juvenile Rheumatoid Arthritis. Rash presentation is different.

Day 2 – (*Consult with Nephrology) SUBJECTIVEOBJECTIVEASSESSMENTPLAN Afebrile 5/10 abdominal pain Cough (-) vomiting (-) loose stool (-) dysuria (-)hematuria (-) joint/muscle pain HR 88 RR 20 BP 90/60 Temp 36 ∘ UO: 3.97 ml/kg Soft abdomen (+) tenderness in LUQ, LLQ, RUQ – resolved later (+) multiple non-blanching, non-pruritic macular rashes on both lower extremities Henoch- Schonlein Purpura Order blood C/S, C3, PT, PTT Hydrocortisone (solucortef) 35 mg per IV every 8 hrs (4mg/kg/dose)

Diagnostic Plan Date HgbHct WBC NLME PLT June June June

Labs Day 2  Complement 3 – 1.39 g/L ( g/L)  Prothrombin Time s (12-14s)  Activated Partial Thromboplastin Type – 32.5s (28-37 s)

Day 3 – AP SUBJECTIVEOBJECTIVEASSESSMENTPLAN comfortable (-) vomiting, fever, abdominal pain, gross hematuria persistent coughing (-) abdominal pain Good oral intake RR 32 UO: 2.27 ml/kg Harsh breath sounds (+) CLAD (+) multiple non-blanching, non-pruritic macular rashes on both lower extremities HSP pneumonia r/o primary Koch’s Order CXR Order PPD Pulmonology consult Start cefuroxime 750 mg IV every 8 hrs for 3 days shifted solucortef to prednisone Urinalysis monthly for the next 6 months No contraindication for d/c if prednisone tolerated

Day 3 – Consult with Pulmonology SUBJECTIVEOBJECTIVEASSESSMENTPLAN awake comfortable persistent cough afebrile RR 18 UO: 2.27 ml/kg (+) CLAD (-) wheeze (-)rales (-)retractions (-) alar flaring CXR: thin linear density on left upper lobe; no other parenchymal infiltrates; the rest normal HSP Viral Pneumonia r/o primary Koch’s Encourage deep breathing exercises Increase fluid intake May give Erdosteine syrup 7.5 ml BID for 5 days Ordered PPD

Labs Day 3 Chest Xray  impression: subsegmental atelectasis versus parenchymal fibrosis, left  Thin linear density seen in the left upper lobe Blood culture  No growth after 24 hours of incubation

Day 4 SUBJECTIVE OBJECTIVE ASSESSMENT PLAN afebrile persistence of cough no subjective complaints (-) abdominal pain HR 72 RR 20 BP 100/60 Temp 36.6 ∘ UO: 1.70 ml/kg (+) palpable non- blanching and non- pruritic macular lesions on both lower extremities harsh breath sounds (-) rales (-) murmurs (-) abdominal pain HSP viral pneumonia r/o primary Koch’s continue management no absolute contraindication for discharge prednisone (Pred 10) at 5ml TID for 5 days; decrease to 5ml BID for 5 days, to 5ml once a day for 5 days, then stop; follow up after 1 week give last dose of cefuroxime IV at 8pm then shift to oral cefuroxime 250mg/5ml, 5ml BID tom am

Day 5 SUBJECTIVE OBJECTIVE ASSESSMENT PLAN no new rashes occasional mild abdominal pain good appetite HR 86 RR 21 BP 90/60 Temp 36.6 ∘ PPD Negative decreased number of palpable non-blanching and non-pruritic macular lesions on both lower extremities pink palpebral conjunctiva Normal heart rate Regular rhythm No retractions Soft, nontender abdomen Full pulses HSP resolving Pneumonia resolving For discharge Follow –up

DIAGNOSIS TREATMENT MANAGEMENT Henoch Schonlein Purpura

Named after 2 German physicians Johan Schönlein  (1837) Associated nonthrombocytopenic purpura and joint pain Eduard Henoch (student of Schönlein)  (1874) described GI and renal manifestations:  GI: vomiting, abdominal pain, melena  Renal: nephritis

Medical Eponyms Rheumatica purpura Anaphylactoid purpura Leukocytoclastic vasculitis Allergic vasculitis

The most common vasculitis in children A subset of necrotizing vasculitis  Fibrinoid destruction of blood vessels  Leukocytoclasis Immunoglobulin A (IgA) Generalized vasculitis  Involves the small vessels of the skin, GI tract, kidneys, joints, and, rarely, the lungs and CNS. Characterized by purpura, arthritis, abdominal pain, and hematuria.

IgA clearly plays a critical role in the immunopathogenesis Increased:  Serum IgA concentrations  IgA-containing circulating immune complexes  IgA deposition in vessel walls and renal mesangium. Exclusively involves IgA1, rather than IgA2. Immune complexes  insoluble  deposited in the walls of small vessels  inflammatory mediators (vascular prostaglandins) Immune complexes (w/ IgA and C3) have been found in skin, kidneys, intestinal mucosa, and joints

Where does the IgA elevation come from? Antigens that may stimulates the production of IgA  vasculitis. Food allergies, drug intake, infectious causes (bacteria and viruses), vaccinations Transforming growth factor–beta (TGF-beta) Gene polymorphism  varied IgA elevations  diversity of clinical responses to inflammatory stimulation. Alterations in the production of interleukins (ILs) and growth factors

Epidemiology In the United States, 75% of HSP are in children aged 2-14 years. The incidence in this age group is 14 cases per 100,000 population. The male-to-female ratio is 1.5-2:1.

Clinical Manifestations Prodrome  As many as 50% of occurrences in pediatric patients are preceded by a URI by 1-3 weeks Clinical manifestations primarily include the following:  palpable purpura  arthralgia or arthritis  abdominal pain  gastrointestinal (GI) bleeding  nephritis.

Hallmark  characteristic palpable purpura Presentation of the purpura  buttocks and upper thighs in younger children  feet, ankles, and lower legs in older children and adults only  Appears in crops with new crops appearing in waves.  Eruptions last an average of 3 weeks. Pathophysiology  Immune complex deposition (IgA, C3) in vessels of the papillary dermis  vessel injury  extravasation of RBCs  palpable purpura.  Occurs in dependent body regions, such as the lower legs, buttocks, back, and abdomen.

Clinical Manifestations Fever  Inflammatory response  Temperature usually not higher than 38°C Arthralgia / arthritis  Presenting complaint (25%) occurs at some point (60-75%)  Ankles and knees (most common) | any joint Abdominal pain  Sharp / colicky  Present in as many as 65% of patients  Secondary to vasculitis-induced submucosal and subserosal hemorrhage and edema, with thrombosis of the microvasculature in the gut.

Clinical Manifestations Hematuria / proteinuria  Mesangial deposits of IgA  subendothelial and subepithelial glomerular spaces.  HSP-associated nephritis  renal manifestations (minimal change to severe crescentic glomerulonephritis)  Most dreaded complication:  Progressive renal failure (1-2% of patients) Others  Testicular pain and swelling  Hepatosplenomegaly  CNS /PNS involvement  Headache  Rare: myocardial infarction / pulmonary hemorrhage.

Supportive Treatment Self-limited  hydration, replacement of blood loss Treat underlying or predisposing factors.  Food allergies  Drug intake  Infectious causes (bacteria and viruses)  Vaccinations

Corticosteroid use: (1) reduce severity or duration of disease  Roseblum et.al, rapid improvement of abdominal pain in 50% w/ corticosteroids vs. 14% (control) (2) decrease the risk of glomerulonephritis  N = 168 || 0/84 patients developed nephropathy (w/ prednisone) vs. 12/84 (control) Summary: Use for possible early treatment of abdominal pain and GI bleeding

Chances of Recurrence Disease recurrence occurs throughout weeks to months in adults and children. Children older than 2 years had a recurrence rate of 50%, while those younger than 2 years had a less than 25% chance of recurrence Better prognosis in younger patients, and those without renal complications

Public Health / Management

SCOAP But who is our patient?  NE from Barangay San Luis, Antipolo City  SES probably B or C  Family with adolescents  Cultural beliefs  Hilot

Hospital Charges Central Processing Unit Laboratory5230 Emergency Room Pharmacy Department Pedia Patients Unit Radiology Department590 Room and board – other unit4500 Satellite laboratory ER5580 Emergency room TOTALPhp 23,857.50

Health Insurance Can the ordinary Pinoy afford to pay his medical bills? Medical insurance is needed in the Philippines  2.2 percent of national budget allocated for health Public hospitals – understaffed and ill-equipped Private hospitals – expensive

Public Health in HSP? Prognosis  self-limited with an excellent overall prognosis  <1% develop renal disease No preventive measures to avoid complications Prevention and treatment of renal disease in Henoch-Schönlein purpura: a systematic review W Chartapisak, S L Opastiraku, N S Willis, J C Craig E M Hodson  Meta-analyses showed no significant difference in the risk of persistent kidney disease at 6 and 12 months in children given prednisone for 14–28 days at presentation HSP compared with placebo or supportive treatment.

Public Health in HSP?

Paradox of Rarity Even though the disease is rare, rare disease patients are many - European Organization for Rare Diseases