Unusual presentation of pica in iron-deficiency anaemia associated with primary biliary cholangitis

Abstract

A 50-year-old woman presented with worsening fatigue and shortness of breath. For 2 months, she has been having increased craving for unpeeled lemons and was seen in clinic about a month prior to presentation at the emergency room. At that time, she was asymptomatic except for endorsing craving for lemons. Physical exam findings at presentation noted obesity, sinus tachycardia, pallor, mild scleral jaundice and no other stigmata for chronic liver disease. Her labs suggested iron-deficiency anaemia (IDA), elevated liver enzymes and positive antimitochondrial antibody titre. Abdominal ultrasound and CT scan showed mild scarring. She was diagnosed with primary biliary cholangitis with portal hypertension complicated by oesophageal varices and IDA. Interventions included blood transfusion, oesophageal banding and treatment with ursodeoxycholic acid. Her craving for lemons, shortness of breath and fatigue resolved within 1 week. With ongoing outpatient follow-up and oesophageal variceal surveillance, she continues to do well.

Background

The name “pica” is derived from the Latin word for the Magpie bird known for its indiscriminatory appetite. This is a complex behaviour that describes excessive and abnormal craving for nutritive and non-nutritive substances¹ often implicated in organic causes, such as iron-deficiency anaemia (IDA),² and in certain sociocultural norms.¹ IDA in primary biliary cholangitis (PBC) may be multifactorial. It is our understanding that only one case of pica presenting with a craving for unpeeled lemons has been reported; there is no term for ‘unusual craving for lemons’ and the incidence and prevalence of adult pica in PBC is unknown. We present this case because of the subtle, non-classical presentation of pica.

Case presentation

A 50-year-old woman with no remarkable medical history presented to the emergency room (ER) for worsening fatigue and shortness of breath for 2 months. She was seen a month prior at the clinic for a routine follow-up and stated she had been eating at least 2 bags of unpeeled lemons daily. A benign overall impression was made after her clinic encounter. She has a family history of haemochromatosis in her father. Physical exam in ER noted obesity, sinus tachycardia, severe pallor and no other stigmata for chronic liver disease.

Investigations

International normalised ratio and immunoglobulin G were within normal limits. She was heterozygous for the C282Y mutation of HFE gene, antimitochondrial antibody (AMA) titre 1:60. A panel for double-stranded DNA, anti-smooth antibody(ab), antineutrophil cytoplasmic ab, HIV, Helicobacter pylori (H. pylori), hepatitis B surface antigen, and hepatitis A, B and C ab were negative. Oesophageal-gastro-duodenoscopy (OGD) showed multiple oesophageal varices including one large column with red spots (figure 1), but no active bleeding. Right upper abdominal ultrasound scan revealed mild irregular contour and scarring of the left lower lobe of the liver and CT of the abdomen showed hepatomegaly, mild nodularity of the liver and was negative for ascites. The patient declined liver biopsy.

Figure 1.

OGD at the time of admission showing oesophageal varices with prominent red spots. OGD, oesophageal-gastro-duodenoscopy.

Differential diagnosis

Our patient met the criteria for PBC with ongoing hepatic workup given elevated liver enzymes (>2 times rise in alkaline phosphatase (ALP) levels and >1:40 AMA) in the setting of positive ANA (1:320, centromere pattern). Antineutrophil cytoplasmic antibody (ab), anti-smooth ab, hepatitis A, C and B core ab, and hepatitis B surface antigen were negative ruling out primary sclerosing cholangitis, autoimmune hepatitis and other infectious hepatitis. Normal acetaminophen, ethanol and salicylate levels along with negative urine drug screen suggested drug-induced/alcohol-induced liver injury to be unlikely. Biochemical evidence of cholestasis with increased serum ALP (table 1) supports PBC as 50%–60% of patients with PBC are asymptomatic.³ Though liver biopsy deferred, ultrasound and CT abdomen findings suggest mild cirrhosis with the absence of hepatic steatosis. OGD showed oesophageal varices, faecal occult blood was positive and colonoscopy revealed transverse and descending 3 mm sigmoid polyps. Diagnosis of IDA is supported by low haemoglobin, iron and ferritin level with elevated total iron-binding capacity and hypochromic microcytosis (table 1).

Table 1.

Initial laboratory results during hospitalisation

Lab	Result	Normal range
Haemoglobin	33	120–156 g/L
MCV	55.5	80–100 fL
RDW	21.1	9%–15%
RBC morphology	Marked microcytosis and hypochromia
Platelet	301× 109/L	130–400×109/L
Iron	24	35–175 μg/dL
Iron saturation	4	12%–57%
Total iron-binding capacity	535	200–450 μg/dL
Ferritin	5	12–156 ng/mL
Bilirubin total	1.3	0.0–1.2 mg/dL
Bilirubin direct	0.6	0.0–0.4 mg/dL
Aspartate transferase	76	0–46 U/L
Alanine transferase	84	0–60 U/L
Alkaline phosphatase	461	23–144 U/L

The aetiology of IDA in PBC may be multifactorial. In our case, it was thought to be mainly from gastrointestinal (GI) haemorrhage from portal hypertensive gastropathy. Other causes can be explained from gastric antral vascular ectasia, peptic ulcer, coagulation defect, colonic polyps and gastritis/duodenitis occurring in isolation or associated with other autoimmune conditions, such as celiac disease, which causes reduced iron absorption. Normal gastric secretion and acidity are important for normal uptake of iron.⁴ Ferric iron precipitates at pH>3 and is absorbed in the ferrous form or chelated form. The incidence of chronic autoimmune gastritis and IDA has been increasingly reported.⁵ Floreani et al in a small cross-sectional study found that chronic gastritis in PBC is not typically characterised by atrophy and are less frequently infected with H. pylori.⁶ Atrophic gastritis should be suspected when IDA remains refractory to oral therapy.

The presence of bleeding oesophageal varices due to portal hypertension is a common cause of IDA in PBC. Ikeda et al in a study in 2012 found that high ALP (OR=2.3) and low platelet counts (OR=0.77) were significantly associated with the presence of oesophageal varices in the patients with early PBC.⁷

Lemons, a source of vitamin C, are not known to be a great source of iron, though vitamin C helps iron absorption. Pica is more likely to cause malnutrition when manifested by consumption of non-nutritive substances. Menstrual iron loss in women of childbearing age is also an important predictor of iron status.

Treatment

Therapy begins with identifying the aetiology of iron deficiency, treating its cause and instituting iron replacement therapy. Our patient underwent banding of oesophageal varices and packed red cells were transfused. Ursodeoxycholic acid and oral iron supplements were initiated prior to discharge from the hospital.

Outcome and follow-up

Her craving for lemons, shortness of breath and fatigue resolved within 7 days, and she appeared to be back to her baseline at her 10 days post-hospitalisation clinic visit. With ongoing outpatient follow-up and oesophageal variceal surveillance, she is doing well.

Discussion

IDA is the most common nutritional deficiency worldwide; it reduces work capacity in adults, causes fatigue and leads to cognitive disorders. Pica remains a fascinating symptom. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, describes pica criteria to be present for at least 1 month prior to diagnosing the disorder in the absence of other psychological-related disorders, such as autism, schizophrenia, intellectual disability or culturally accepted eating behaviour. Coltman in 1969 describes pica subtypes based on the substance eaten: geomelophagia (raw potatoes), pagophagia (ice), amylophagia (starch), emetophagia (vomit), hyalophagia (glass), lithophagia (stones), mucophagia (mucus), urophagia (urine), xylophagia (wood), coprophagia (faeces), geophagia (dirt, soil and clay) and trichophagia (hair).⁸ Johnson and Stephens in 1982 discussed a compulsive eating of raw chilled potatoes (geomelophagia) in a patient with IDA and lung cancer.⁹ The abnormal craving is not always for a strange article, this case hopes to shed light on a craving for ordinary food associated with iron deficiency. Typically, the presentation of pica involves the ingestion of ice cubes, sand, clay and other non-nutritional substances. Only one case of pica for unpeeled lemons has been reported (2008).¹⁰ IDA is not the only cause of PICA; pregnancy and cultural practices are among others. The prevalence of pica is unknown because it is believed to be under-reported due to ethnic–cultural practices¹¹ and patient embarrassment.² Pica is caused by iron deficiency, not necessarily by anaemia itself,¹¹ as cases have been reported of pica in the absence of anaemia.^12–14

Screening for GI bleeding is indicated even in the absence of overt bleeding in PBC since affected patients are at risk of severe portal hypertension due to nodular regenerative hyperplasia of the liver despite normal bilirubin levels and absence of cirrhosis on liver biopsy.¹⁵ Therapy begins with identifying iron deficiency and instituting iron replacement therapy. If not suspected, pica symptoms can go unnoticed.^{16 17} Pica from iron deficiency will remit with time following iron replacement. In cases of refractory pica, selective serotonin reuptake inhibitors^{18 19} and a formal mental health referral for behavioural intervention may be beneficial.²⁰

Patient’s perspective.

This experience remains quite scary but yet funny to me. At one point, I was commended for eating healthy and making good dietary choices. It seemed to me that I lost a few pounds too, the first wrong sign I felt was tiredness, which was attributed to stress. That fateful day, I went to the ER, I was in bed for almost the whole day prior, sleeping at every chance that I get, my family was concerned and encouraged me to go to the hospital. Then the scary part began, first, I found out my blood level was low and I needed blood, then I had abnormal liver lab work. Later, I was informed that there may have been bleeding deep down in my throat as well. What a relief to hear that my condition could be treated with medication. In retrospect, I think I craved celery as well, now I have gained a few more pounds since my appetite returned and feel great overall.

Learning points.

• Pica should be suspected when there is a history of abnormal craving for not only non-nutritive but ordinary food as well.

• Iron-deficiency anaemia is a common cause of pica, which must be investigated if pica is suspected.

• Primary biliary cholangitis patients are screened for gastrointestinal bleed by performing oesophageal-gastro-duodenoscopy.