Iron deficiency (ID) is more frequent than ID anemia [1] and between 2 -5% of postmenopausal women and adult men suffer from ID anemia [2] [3]. ID develops when the iron intake falls short of the iron requirements of the body (pregnancy, adolescence) or when the output of iron exceeds the intake (gastrointestinal bleeding).

ID often presents insidiously with non-specific symptoms like tiredness, poor immunity to infections and low exercise tolerance. The incidence of ID is more common in premenopausal women due to menstrual blood loss while in pregnancy, adolescence and during breastfeeding, ID is due to increased requirements of iron. ID can lead to increased fatigability, especially in women [4] [5] [6]. Athletes are also at risk of iron deficiency as studies have shown urinary loss of iron following repeated minor intravascular hemolysis [7] [8]. ID can lead to anemia which can present with koilonychia, atrophic glossitis, fissured tongue, angular cheilitis, pica, pallor, decreased intellectual abilities, dyspnea, hepatosplenomegaly (in hemolytic anemias), high output cardiac failure, and recurrent upper respiratory tract as well as other infections. Chronic diseases like celiac disease, chronic renal failure, cirrhosis and even cancers can be associated with ID with patients manifesting symptoms and signs of these conditions. Gastrointestinal tract bleeding is another potential presenting feature in individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) over long periods of time or in those with malignancies of the gastrointestinal tract.

• Fatigue

  Iron-Rich Foods to Fight Fatigue To fight fatigue that's caused by an iron deficiency, turn to iron-rich foods. By changing your diet, you could see significant changes in your energy level within as little as one week. [doctoroz.com]

  Abstract We report a case in an adolescent male patient with a history of chronic fatigue, headache and unexplained iron deficiency anaemia since 2007. Numerous bluish-black lesions were found over his body surface. [ncbi.nlm.nih.gov]

  Iron loss can contribute to a multitude of health problems – not just fatigue. [glutenfreesociety.org]

• Pallor

  A thorough physical examination to identify features of ID and ID anemia like pallor, koilonychia, glossitis and even high output cardiac failure should be performed. [symptoma.com]

  Anterior segment examination in both eyes showed conjunctival pallor. Results of ophthalmoscopic examination and optical coherence tomography were consistent with macular preretinal hemorrhage in both eyes with macular star in the left eye. [ncbi.nlm.nih.gov]

  Clinical history, presentation, and findings include fatigue, pallor, dyspnoea on exertion, and pica. Microcytic, hypochromic anaemia; low reticulocyte count. [bestpractice.bmj.com]

  Symptoms include weakness, fatigue, and sometimes pallor, shortness of breath, coldness of extremities, changeable appetite, sore tongue, loss of hair, brittle fingernails, or dry skin. [britannica.com]

  At necropsy, these pigs will have pallor, a thin-walled heart, and edema of the lungs, muscles and connective tissues. [vetmed.iastate.edu]

• Exertional Dyspnea

  Typical anemia symptoms include: Fatigue, weakness Irritability Exercise/feeding intolerance Exertional dyspnea Headache, vertigo Pale skin Symptoms of iron deficiency include: Pica (craving of non-food items – such as clay, dirt, paper, ice, baby powder [danafarberbostonchildrens.org]

  dyspnea, fatigue, weakness, and tachycardia.[15] It may lead to heart failure.[15] Anaemia is often a cause of dyspnea. [en.wikipedia.org]

• Abdominal Pain

  Inflammatory bowel disease -Diarrhea, abdominal pain and mucous in your bowel movements are caused by inflammation (swelling and redness) of the lining of the colon. This may cause rectal bleeding. [chemocare.com]

  In patients describing dysphagia, gastritic symptoms, nausea, vomiting, or upper abdominal pain upper GI lesions should be suspected. [clinicaladvisor.com]

  The specific lower gastrointestinal symptoms inquired about included hematochezia, a change in bowel habits, diarrhea, constipation, and lower abdominal pain that was colicky or changed with the passage of stool. [doi.org]

  This dose is rather high, and can lead to nausea, diarrhea, or abdominal pain in 10-20% of women taking this dose. [medical-dictionary.thefreedictionary.com]

• Fissured Tongue

  ID can lead to anemia which can present with koilonychia, atrophic glossitis, fissured tongue, angular cheilitis, pica, pallor, decreased intellectual abilities, dyspnea, hepatosplenomegaly (in hemolytic anemias), high output cardiac failure, and recurrent [symptoma.com]

• Alopecia

  […] dirt, paper, ice, baby powder, starch) Poor sleep or restless leg syndrome Angular cheilitis (sore lesions at the corners of the mouth) In rare cases, children with iron deficiency anemia may also experience: Nail changes (koilonychia or spoon nails) Alopecia [danafarberbostonchildrens.org]

• Photosensitivity

  […] an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity [ncbi.nlm.nih.gov]

• Headache

  Abstract We report a case in an adolescent male patient with a history of chronic fatigue, headache and unexplained iron deficiency anaemia since 2007. Numerous bluish-black lesions were found over his body surface. [ncbi.nlm.nih.gov]

  Headaches Headache, especially with activity, can be a sign of iron deficiency. Unfortunately, a headache is also a symptom people often ignore even though it can sometimes be life-threatening. [msn.com]

  Other symptoms of the condition include spoon shaped or scooped nails, breathlessness, loss of consciousness, an irregular heartbeat, headaches, and dizziness. [the.ismaili]

  Symptoms include: Fatigue Pale skin and fingernails Weakness Dizziness Headache Glossitis (inflamed tongue) Sources of Iron The body absorbs two to three times more iron from animal sources than from plants. [eatright.org]

• Vertigo

  Typical anemia symptoms include: Fatigue, weakness Irritability Exercise/feeding intolerance Exertional dyspnea Headache, vertigo Pale skin Symptoms of iron deficiency include: Pica (craving of non-food items – such as clay, dirt, paper, ice, baby powder [danafarberbostonchildrens.org]

ID can develop insidiously with or without anemia. Therefore early diagnosis of the condition is difficult. In all patients, a detailed history of symptoms, history of chronic intake of NSAIDS and blood loss in urine or stools or excessive menstrual blood loss should be obtained. NSAID enteropathy is associated with significant amounts of blood loss [9]. A thorough physical examination to identify features of ID and ID anemia like pallor, koilonychia, glossitis and even high output cardiac failure should be performed.

Routine laboratory tests like complete blood count, hemoglobin levels, hematocrit, urinalysis for hematuria and stool test for occult blood as well as other tests like liver enzymes, renal function tests, echocardiography are indicated depending on the history and physical examination findings. Specific tests for iron deficiency detection include serum ferritin, serum iron, and transferrin saturation.

Tests to detect the cause of the ID include celiac disease serology, gastroscopy and colonoscopy [1]. Repeated endoscopies or capsule endoscopies may be necessary to detect persistent ID [1].

1. Bermejo F, Garcia-Lopez S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. Worl J Gasteroenterol. 2009 Oct 7;15(37): 4638 -4643
2. Goddard AF, McIntyre AS, Scott BB. Guidelines for the management of iron deficiency anaemia. British Society of Gastroenterology. Gut. 2000;46 Suppl 3-4:IV1–IV5.
3. Sayer JM, Long RG. A perspective on iron deficiency anaemia. Gut. 1993;34:1297–1299.
4. Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012;184:1247–1254.
5. Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326:1124.
6. Krayenbuehl PA, Battegay E, Breymann C, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011;118:3222–3227.
7. Peeling P, Dawson B, Goodman C, et al. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol. 2008;103:381–391.
8. Robertson JD, Maughan RJ, Davidson RJ. Faecal blood loss in response to exercise. Br Med J (Clin Res Ed) 1987;295:303–305.
9. Bowen B, Yuan Y, James C, et al. Time course and pattern of blood loss with ibuprofen treatment in healthy subjects. Clin Gastroenterol Hepatol. 2005;3:1075–1082.