Clinical application of basic concepts of pallor is not equivalent of anaemia, though in routine practice, pallor is mostly due to anaemia. Dr. YK Amdekar in this part discusses various patient presentations and appropriate diagnosis and treatment.

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Before you begin, take this quick quiz to test your knowledge of pallor.

Acute severe anaemia presents as shock as happens in case of large amount of blood loss while chronic severe anaemia may present as congestive cardiac failure. Slowly progressive anemia may be well compensated without cardiac dysfunction.

Three major groups of diseases present with anaemia – deficiency, haemolysis and bone marrow dysfunction. It is possible to differentiate these groups by history and physical examination. CBC and peripheral blood smear are excellent screening tests that nearly confirm group diagnosis. Further specialised tests may be necessary to define the subgroup and make a final diagnosis. This approach helps to minimise laboratory evaluation instead of ordering a battery of tests.

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Case 1

A 1-year old child presented with pallor noticed by the mother over the last few weeks. There were no other significant symptoms. He was exclusively breastfed for the first 6 months and thereafter, the mother introduced diluted cow milk while continuing breast feeds and occasional cereal.

As there were no symptoms other than pallor, it appeared to be chronic severe anaemia. Absence of jaundice mostly rules out haemolytic anemia (though thalassemia major has no jaundice). In the absence of purpura (indicating low platelets) and any significant sickness, bone marrow disease was not possible. This leaves us with deficiency anaemia. This child only consumed milk that is poor in iron and so this was mostly iron deficiency anaemia.

Physical examination showed not sick-looking, pallor ++, koilonychias +, weight of 8.5 kg, length 74 cm (both normal meaning that this is getting enough calories and proteins), normal temperature , HR 120 RR 28 (mild proportionate increase in heart and respiratory rate in the absence of fever suggesting mild strain on the heart), liver 3F +, firm, not tender, liver span 8 cms, spleen not palpable, signs of rickets+

This child had signs of iron deficiency anaemia as suggested by koilonychias and also had rickets. Milk is a poor source of both iron and vitamin D and hence it seemed compatible with our thinking. However, deficiency anaemia does not present with hepatomegaly. Considering mild increase in HR and RR, it denoted congested liver though without congestive cardiac failure yet. This child would have presented with cardiac failure if not treated.

Thus, the clinical diagnosis was iron deficiency anaemia on the brink of cardiac failure. The blood smear showed microcytic hypochromic anaemia with low MCV and high RDW, characteristic of iron deficiency anaemia. There was no need to further confirm with serum iron studies.

The oral iron supplement with ferrous sulphate is ideal (choice depends on tolerance in individual child) and will show rise of one gram of Hb in one week.

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Case 2

A 2-year-old child presented with severe pallor and no other symptoms. Six months ago, he was seen for severe pallor for which blood transfusion was given without arriving at any definite diagnosis. He was exclusively breast-fed for the first 5 months and then the mother started complementary feeds gradually increasing to a family vegetarian diet over the next 6 months. After the age of one year, he was on family food with small amounts of cow milk. He had grown well over the last two years. The was no family history of similar disease. There was no history of consanguinity.

This child had recurrent anaemia despite one blood transfusion 6 months ago for similar complaints. The recent episode after analysing suggested deficiency anaemia because of absence of any other symptoms suggestive of either haemolytic anemia or bone marrow involvement. He was consuming very little milk after the first 6 months of life though he was on full family diet. The lack of dairy products in a vegetarian family diet runs a risk of vitamin B12 deficiency. So this may be B12 deficiency anaemia. However, the odd point was the recurrence of anaemia within 6 months. This was explained based on the absence of B12 supplementation during the last episode wherein blood transfusion improved his hemoglobin temporarily only to go down again.

Physical examination showed comfortable child not sick-looking, weight of 11 kg, length 87 cm, pallor ++, pigmented knuckles, mild icterus, no abnormal facies, liver and spleen not enlarged and other systems normal.

Severe anaemia without hepatosplenomegaly in a comfortable child with pigmented knuckles suggests B12 deficiency anemia. However, the odd point was the presence of icterus that is normally seen in haemolytic anemia. The absence of enlarged liver and spleen and abnormal facies (due to extra-medullary haemopoiesis) ruled out haemolytic anaemia.

Five percent of B12 deficiency anaemia patients may have mild jaundice though most of them don’t. So, diagnosis was stayed to be vitamin B12 deficiency anaemia. This was suggested by macrocytic anaemia with increased MCV and RDW and further confirmed by serum vitamin B12 level.

Ideal treatment consists of parenteral vitamin B12 as oral absorption may be erratic due to insufficient intrinsic factor in the stomach. As this child was not treated with Vitamin B12 last time, anaemia recurred.

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Case 3

A 2-month-old infant presented with pallor noticed since one month and focal seizure involving left upper limb one hour prior to hospitalisation. There was no jaundice or purpura or bleeding. He was born after full term with forceps delivery. The baby cried immediately and was on breast feeds throughout.

Anaemia in a two-month-old infant is not a deficiency anaemia as the foetus derives all the nutrients from the mother that lasts for a few months after birth and continued exclusive breast feeds will nourish the infant ideally. This was a full term infant and not preterm who may present with anaemia so early in life due to short period of nutrient transfer from mother to foetus. It is also unlikely that this was haemolytic anemia as it would present with jaundice. It may therefore be bone marrow problem, however there was no clue in the absence of purpura or bleeding (due to thrombocytopenia). With this discussion, one was not sure about the type of anaemia on history alone.

Focal seizure suggested space occupying lesion in the motor cortex. Brain tumors are rare at this age and so correlating with anaemia, this may be a haematoma – could be attributed to trauma caused by forceps delivery. Such a haematoma may account for loss of blood and hence, anaemia. Typical subdural haematoma may accumulate blood over time to lead to anaemia as well as focal seizure.

Physical examination showed a conscious infant, weight of 3.5 kg (birth weight 2.5 kg), length 55 cm, head circumference of 40 cm, pallor ++, no icterus, liver 2F +, soft, spleen not palpable, mild weakness of left upper limb, anterior fontanale mildly boggy suggesting mile increased intracranial tension.

Anaemia without hepatosplenomegaly or purpura and comfortable infant suggested deficiency anaemia a result of slow progressive subdural bleed. Hence, diagnosis of subdural haematoma with significant anaemia was certain. It can be proved by USG of skull (CT scan may not be necessary) and deficiency anaemia by CBC and peripheral smear. It is worth noting that deficiency anemia may result from slow bleeding anywhere in the body, at times bleeding is hidden – commonly in intestines as in hook work infestation or any other bleeding such as polyposis.

Treatment requires evacuation of haematoma and antiepileptic drug such as phenobarbitone for about 6 months and iron supplements.

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Case 4

A 2 months old infant presented with pallor noticed since a few days and irritable since then, reluctant to feed. The child had been born after full term normal delivery and had been on exclusive breast feeds.

The infant had been sick as was evidenced by the loss of appetite and presence of irritability and had presented with a recent onset of anaemia. It was obviously not a deficient anaemia at this age and also unlikely to be congenital haemolytic anaemia as the infant was sick. So most likely this was bone marrow disease – either aplastic anemia or any other infiltrative disorder such as leukemia.

Physical examination showed sick-looking infant, weight of 4.3 kg, length 53 cm, head circumference of 39 cm, pallor++, liver 2 F+, soft, spleen just palpable, deformity of left forearm This anaemia was without hepatosplenomegaly (liver 2 f+ and spleen just palpable at this age is within normal limits) in a sick irritable infant with congenital malformed limb suggested congenital aplastic anaemia. Presence of any congenital malformation seen on physical examination demanded search for any other malformations that may as well be hidden. So, the clinical diagnosis was congenital aplastic anaemia.

CBC showed pancytopenia and diagnosis confirmed by bone marrow aspiration. There is no specific drug treatment and marrow transplant is indicated.

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Case 5

A 6 years old child presented with a lump in the left upper quadrant of the abdomen, feeling fatigued since a few months. Past history indicated one episode of severe abdominal pain lasting for a day that settled down by itself without definite diagnosis. There was history of consanguinity.

The lump in the left upper quadrant of the abdomen suggested an enlarged spleen and fatigue over a few months indicated chronic anaemia. Chronic anaemia with splenomegaly was either due to haemolytic anaemia or bone marrow disease such as leukaemia or storage disorder. One episode of severe abdominal pain that lasted for a day does not suggest colic.

Abdominal pain may be inflammatory, vasogenic, neurogenic, referred or psychogenic. Inflammatory pain was not possible as there were no symptoms of inflammation and neurogenic pain was ruled out as it was localised to the direction of a nerve. So, this may be vasogenic pain. Bone marrow disease would not cause vasogenic pain while haemolytic anemia that may cause vasogenic pain is sickle cell disease. Thus, diagnosis of sickle cell anemia was most likely. The history of consanguinity favoured such a diagnosis.

Physical examination showed weight 18 kg, height 102 cm, pallor +, liver 3F+, not tender, spleen 4F+, firm, no icterus, no ascites, rest of the systems normal. It supported diagnosis of haemolytic anaemia in view of hepatosplenomegaly with anaemia, but without jaundice.

Jaundice in haemolytic anaemia is classically seen in congenital spherocytosis and acquired autoimmune haemolytic anaemia. Jaundice is absent in thalassemia. However, sickle cell disease may affect liver and cause jaundice that is not haemolytic but due to the liver being affected. Thus, diagnosis in this child was sickle cell anaemia.

Diagnosis can be confirmed by haemoglobin electrophoresis that would show haemoglobin S. It is called sickle cell anaemia because RBCs are sickle shaped instead of spherical that impedes smooth flow of blood in the capillaries. Treatment is symptomatic.

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Case 6

A 4 years old child presented with fever and irritability for one week and pallor noticed over the previous two days. There were no other complaints. The child was well prior to the onset of symptoms.

Fever suggested either infection or inflammation. Viral infection presented with cold, cough and was most often self-limiting, so it was unlikely. Bacterial infection usually has localising symptoms which this child did not have. So, it may be non-infective illness. Pallor indicated haematological illness and irritability which may suggest pain that was not localised, but likely to be generalised. Generalised pain may be either muscle or bony pain. Pallor with bony pain may indicate possibility of leukaemia.

Physical examination showed a sick-looking child, irritable, pallor++, liver 4F +, soft, not tender, spleen 2F +, large cervical lymph nodes on both sides, firm, not tender. In view of hepatosplenomegaly and lymphadenopathy with pallor, acute lymphoblastic leukemia was most likely.

Diagnosis was confirmed by peripheral blood smear showing blast cells along with low haemoglobin and platelet count with lymphocytosis and if necessary, by bone marrow examination. Further studies are necessary to define more details for which specialised tests are necessary. These specialised studies can help with tailor-made chemotherapy and help in prognostication.

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Case 7

A 2 years old child presented with gradually increasing pallor over the previous four months and deviation of angle of mouth noticed over the previous two days. He had been otherwise well.

Pallor in this child may be due to deficiency anaemia, haemolytic anaemia (without jaundice) or chronic bone marrow disease due to storage. Deviation of angle of mouth suggested facial nerve palsy. In the absence of any other neurological symptoms, facial nerve must be involved at its exit from the skull or beyond. If it is at the exit, it must be due to compression of enlarged bone while if it is due to lesion beyond exit, it may be unrelated to anaemia.

The general rule is to ascribe all symptoms to a single disease and hence it may be safe to assume that facial nerve was caught at its exit from the skull due to an enlarged bone. The bone may be enlarged due to abnormal storage in the bone as happens in osteopetrosis.

Physical examination showed a comfortable child not sick-looking but stunted, pallor ++, liver 4F+, not tender, spleen 2F +, lower motor neuron facial palsy. Anaemia with hepatosplenomegaly in the absence of icterus and abnormal facies ruled out haemolytic anaemia and favoured bone marrow storage disease. So, mostly osteopetrosis in which the bone is thickened that leads to compression of cranial nerves leaving the skull bone.

Diagnosis can be confirmed by X-rays showing dense bony structure without differentiation between cortex and marrow cavity. There is no specific treatment and transplant is the only possibility.

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Case 8

An 8 years old child presented with gradually progressive abdominal distension, loss of appetite and weight over the previous 6 months and pallor noticed over the previous two months.

Progressive abdominal distension over long periods suggested enlarged liver alone or with enlarged spleen. Any other space occupying lesion was also possible such as tumour or cyst. Loss of appetite and weight denoted catabolic state often representing generalised disease. Absence of fever ruled out infective or inflammatory disease. Pallor indicated anaemia that had developed over the previous two months and suggested complication of generalised disease now affecting bone marrow. Thus, this was most likely to be storage disorder due to abnormal metabolism. Exact nature of storage was not possible to define on history or physical examination.

Physical examination showed weight 18 kg, height 105 cm, pallor ++, no icterus, liver 5F +, firm, not tender, spleen 5F + firm. This child was undernourished and stunted suggesting chronic catabolic disease involving liver and spleen and lately affecting bone marrow as well. It favoured storage disorder.

Further specialised tests can prove exact metabolic defect. One of the common storage disorders at this age is Gaucher’s disease, the result of specific enzyme deficiency. It can be treated with enzyme replacement.

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To read the first part of this article, click Pallor- How to approach?

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.