Stages of iron deficiency anemia

Clearly, as iron deficiency develops, it will go through various stages, each with its own pattern.

1. IN THE EARLIEST STAGE, iron is gradually being lost from the stores. The serum iron studies are still normal, the FBC appearance is normal. This is called LATENT IRON DEFICIENCY, and there is no specific clinical or laboratory feature to suspect it. It is only if a bone marrow aspirate were done – and clearly there would not normally be any indication for doing it – that one would see that stainable iron and sideroblasts are reduced, and ultimately absent. If one were really suspicious about the possibility of latent iron deficiency, one would still need considerable justification for submitting a patient to aspiration. However, red cell protoporphyrin levels (increased) are an acceptable substitute. Transferrin receptor levels are raised, and the RDW at this stage is still normal. As indicated above, this stage can last for a very variable time, depending on the balance between

a) The rate of blood loss and 

b) The amount of dietary iron (and in what form), the efficacy of absorption, and the quality of the bone marrow

2. Once IRON STORES ARE DEPLETED, the following changes are seen:

a) Serum iron decreases steadily.  

b) Transferrin increases steadily. 

c) % Saturation falls steadily. 

d) Stainable iron and sideroblasts are absent from the marrow. 

e) The RDW rises. 

f) A right shift of the neutrophils gradually develops.

3. It is only now that IRON DEFICIENCY AS SUCH is established:

a) The % saturation is well below 15.

 b) The red cells become microcytic. 

c) The red cells start off by showing anisochromia then full-fledged hypochromia. 

d) The RDW tends to diminish. 

e) Plus the other changes as mentioned before.

Clinical case 1

An 8-month-old boy presents to the emergency department with a rightsided facial droop for 1 day and blackish bruising around both his eyes resembling raccoon eyes for a week. His mother reports that the childhadfallenfromacouch2weeks earlier. The child has also been fussy, withdecreasedfeedingfor3days.He has no history of fever, and findings from a review of his systems are otherwise unremarkable. Medicalhistory, family history, and social history are also unremarkable. On examination, the child is fussy but alert. Vital signs are normal: temperature, 98.7°F (37.0°C); heart rate, 108beatsperminute;respiratoryrate, 32 breaths per minute; and blood pressure, 98/60 mmHg. Anterior fontanelle is soft and flat. There is right-sided ptosis and drooping of the right side of the mouth, especially apparent when the child cries. There arenootherfocaldeficits,andtherest of the neurologic examination findings are normal. Ecchymoses are seen extending, approximately a centimeter, circumferentially around both eyes. The liver is firm and palpable 3 cm below the right costal margin. The rest of the physical examination findings are normal. Initiallaboratoryevaluationreveals the following: hemoglobin, 7.7 g/dL (77 g/L); mean corpuscular volume, 80.7 fL; white blood cell count, 12,390/mL (12.39 109/L); and platelet count, 298 103/mL (298 109/L). Computed tomography (CT) of the head without contrast revealsnoevidenceofintracranialbleeding. Further investigations reveal an

explanation for the child’s constellation of symptoms and anemia.

   What do you think these investigations which have been requested?

What is your diagnosis?


ANSWER



The findings of raccoon eyes, normocytic anemia, and hepatomegaly prompted abdominal ultrasonography, followed by CT of the abdomen and pelvis with contrast, which revealed a left suprarenal mass and masses in the liver suggestive of metastasis. 

Excisional biopsy of the mass confirmed the diagnosis of neuroblastoma with favorable histologic features, and there was no amplification of the N-myc gene. 

Urine catecholamine studies revealed elevation of the vanillylmandelic acid to creatinine ratio, homovanillic acid to creatinine ratio, and dopamine to creatinine ratio.

Bilateral bone marrow biopsies revealed metastatic neuroblastoma.

 A meta-iodobenzylguanidine scan revealed marked uptake in the temporal bones bilaterally, which explained the right facial nerve paralysis. The scan also showed increased uptake in the liver, left suprarenal mass, skull base, ribs, vertebral column, and the long bonesoftheupperandlowerextremities. These findings confirmed the diagnosis of a stage IV neuroblastoma.

 Facial nerve paralysis is most commonly idiopathic, in which case it is called Bell palsy. 

Known causes of nerve VII paralysis include the following:

 (1) infections such as herpes zoster reactivation, herpes simplex virus, Lyme disease, and human immunodeficiency virus


 (2) central nervous system disorders such as stroke and Guillain-Barre syndrome

(3)conditions such as mastoiditis and cholesteatoma
 (4) neoplasms such as parotid gland tumors,centralnervoussystemleukemia, and tumors with central nervous metastasis

(5)sarcoidosis(Heerfordtsyndrome)
(6) head injury. 

Raccoon eyes or bilateral ecchymoses are a classic presentation of neuroblastoma, seen because of periorbital hemorrhage caused by orbital metastasis. However, raccoon eyes are most commonly caused by basal skull fractures or basilar head bleeds and should raise a red flag for child abuse.

 Normocytic anemia in infancy can be due to transient erythroblastopenia of infancy, bacterial or viral infections, hemorrhage, red blood cell membrane or enzymatic defects, bone marrow disorders, and hemolysis due to hemoglobinopathies. Isolated normocytic anemia should also raise suspicion for a malignant tumor as in our patient, who likely had hemorrhage in his tumor.

Pediatric clinical cases

A 3-year-old girl presented to A
þ E with a 1 week history of general flu-like illness and a 1 day history of painful erythematous nodules on her shins. She had no significant past medical history. Her grandfather had previously had HSP but there was no other family history. There was no history of foreign travel and she was not in regular contact with animals. On examination she was miserable and pale but well-nourished and refusing to weight-bear. She screamed if anyone went near her legs. The rest of the examination was normal.
Blood tests showed raised inflammatory markers: CRP 107, WCC 21, Neutrophils 15.5. CXR was unremarkable.
Q1. What is this rash?
a) HenocheSchonlein purpura
b) Chicken Pox
c) Discoid eczema
d) Erythema nodosum
e) Erythema multiforme
Q2. What are the causes of this rash?
a) Inflammatory Bowel Disease
b) Streptococcal infection
c) Sarcoidosis
d) Campylobacter
e) Salmonella
Q3. Choose True or False for the following statements:
a) These lesions leave scars
b) They may continue to erupt for 10 days
c) The lesions usually resolve within a week
d) The lesions are prone to ulceration

e) It is a disorder of the subcutaneous fat


answer


A1 d) This rash is Erythema nodosum. It is a type of pan-niculitis. There is often no obvious cause. The most common cause in children is a streptococcal infection, specifically group A streptococcus secondary to tonsillitis. The nodules can appear 2e3 weeks after a streptococcal throat infection.
This child was treated with IV Augmentin and within 2 days the rash started to fade and the pain eased. A throat swab grew Group A Streptococcus.

A2 a,b,c,d,e) Causes: Streptococcal infection Sarcoidosis
Inflammatory Bowel Disease Pregnancy Tuberculosis Chlamydia

Mycoplasma pneumoniae Yersinia enterocolitica Salmonella Campylobacter
Drug reaction: antibiotics or the combined oral contraceptive pill
Lymphoma and leukaemia
Erythema nodosum is rare. It affects between two and three people in every 10,000 people per year in the UK. It is most common between the ages of 20 and 35 but it can occur at any age.
Usually the first sign of erythema nodosum is flu-like symptoms. 

This happens before the nodules appear and may make a child feel generally unwell for a few weeks. Possible symptoms include a fever, a cough and even weight loss. They may also have aching joints, stiffness and general aches and pains. Their joints may become swollen. Ankle, knee and wrist joints are most commonly affected but any joint can be painful. Aching legs and joints can last for a number of weeks, or even months, after the nodules have appeared.
The nodules (rounded lumps) that occur in erythema nodosum can measure between two to six centimetres across. The shins are the most common site. Other common sites are on the arms, thighs and trunk but nodules can occur anywhere on the body.

Each nodule tends to last for about 2 weeks but new nodules can continue to appear for up to 6 weeks. When the nodule first appears it is usually red, hot and firm to the touch. As the nodule begins to fade, it looks more like a bruise, turning blue and then yellowish. It usually takes some weeks for the nodules to heal completely. They do not leave any scarring

Clinical Pediatric Casess

A 22-month-old girl with no significant co-morbidities presented to Paediatric
 ER with a history of 36 hours of diarrhoea and vomiting associated with a 2 minute toniceclonic seizure with associated eye-rolling and post-ictal phase at home. On arrival to 
 ER she proceeded to have two further 2 minute toniceclonic seizures within 2 hours of the first. She had profuse diarrhoea and vomiting. She had been seen twice previously in hospital for Bronchiolitis and Viraleinduced wheeze. She had no known allergies, no recent travel abroad and was up to date with her immunisations. Her paternal aunt had febrile seizures as a child. There were no developmental concerns.
On examination she was afebrile throughout her time in A
þ E, well perfused with a CRT of less than 2 seconds, heart rate of 160 and respiratory rate of 40. Her general examination was normal however she had a GCS of 14 and was floppy in a post-ictal state.
She was admitted for a fluid challenge requiring continuous NG dioralyte and proceeded to have short generalised toniceclonic seizures about every 90 minutes on the ward. Bloods including glucose were normal. After the eighth seizure she had a CT head and LP which were normal. 48 hours into the illness she proceeded to have a generalised toniceclonic seizure lasting 7 minutes followed by increased tone on the right side in both upper and lower limbs. She was treated with buccal midazolam followed by IV Lorazepam 10 minutes later. After another 30 minutes with ongoing hypertonia on right side she was started on Phenytoin. She was started on IV Ceftriaxone and Aciclovir. After 2 hours the seizure ceased and she had no further seizures. She had been having seizures for a total of 24 hours.
Q1. What is the most likely cause for her seizures?

a) Febrile convulsions
b) Epilepsy
c) Meningitis
d) Rotavirus

e) Herpes Encephalitis

Q2. What type of seizures can occur in this condition?
a) Symmetrical seizures
b) Generalised seizures
c) Partial seizures
d) Partial seizures secondarily generalised
e) Absence seizures

Q3. Over what period of time do the seizures characteristically occur in this condition?

a) 12 hours
b) 24e48 hours
c) 3e5 days

d) 1 week


Answer

A1. Rotavirus
A2. aed
A3. 24e48 hours


A stool sample came back as positive for Rotavirus. Rota-virus is well documented to cause short seizures both generalised and focal, however case reports of status epi-lepticus are rare in afebrile children with rotavirus and is an important part of counselling parents whose children have gastroenteritis symptoms and present with seizures. Previous Asian studies have shown an incidence of afebrile seizures in children being 2.06% with the highest incidence being between 1 and 2 years (4.67%). These seizures most commonly happened on the third day of diarrhoea, typically
in a cluster lasting 24 hours with no status epilepticus reported. Seizures are usually symmetrical and generalised. However partial seizures and partial seizures secondarily generalised have also been described. Over the last 3 years non-Asian studies have been published showing similar results with a mean age of 17 months and maximum seizure duration lasting 10 minutes over 24-48 hours.

Children with rotavirus gastroenteritis are a frequent presentation to most paediatric units. Rarely they are noted to have short self-resolving seizures and parents can be counselled appropriately regarding this complication. It is very unexpected for a patient with no other co-morbidities who is afebrile to develop status epilepticus as a complication of rotavirus gastroenteritis and therefore patients are not usually counselled about this. Recognising this clinical picture and what it is helps to calm both the physician and the patient’s family, given the anxiety-provoking nature of clustered convulsions.