Report of Four Cases With Oral Manifestations

Recognition and management of vitamin B12 deficiency: Report of four cases with oral manifestations Abstract Vitamins are organic compounds present in low concentrations in food, performing vital and specific cell metabolism functions. Vitamin B12 is essential for red blood cell formation in the bone marrow and its deficiency is caused, mainly, by gastrointestinal malabsorption. In addition to systemic manifestations, oral signs and symptoms have also been associated to this condition such as glossitis, papillary atrophy, painful erythema areas, burning sensation, dysgeusia, lingual paresthesia and itching. This study aims to report four cases of oral manifestations caused by vitamin B12 deficiency. All patients presented oral mucosa lesions. Vitamin B12 deficiency was diagnosed based in clinical characteristics and complementary exams. Oral supplementation for vitamin B12 deficiency was conducted/realized in three patients, while one patient was treated with parenteral doses. All of them showed partial or total remission of the signs and symptoms. 1 INTRODUCTION Vitamin B12, also called Cobalamin, is a compund essential for hematopoietic stem cells formation in bone marrow. Previous studies have reported that this mineral is an important nutritional component associated with oral health. Although, the deficiency of Cobalamin is related to some oral manifestations. This event is caused mainly by a decrease in gastrointestinal absortion due to medical condition such as gastrectomy, self-immunity, strict vegetarian diets, gastritis, gastric cancer and the use of medication such as metformin and omeprazole.1 Low levels of B12 can affects specially the cells presenting high cell division rates such as stem cells produced by bone marrow and gastrointestinal epithelial cells. Thus, hematological, gastric, cutaneous and peripherical neurological/neuropsychiatric manifestations may appear.2,3 Oral manifestations of Cobalamin deficiency have been previously related and can appear up to 10 years after its onset due to its considerable hepatic storage. Glossitis, papillary atrophy, painful erythema areas, burning sensation, dysgeusia, lingual paresthesia and itching are the main oral manifestations.4,5 In this context, the present study aims to report four cases of patients presenting vitamin B12 deficiency with oral mucosa manifestations and discuss the differential diagnoses and conducts adopted in relation to patients with this condition. F I G U R E 1 (A) Initial clinical patient aspect, presenting an erythematous and depapillated area on the back of the tongue. (B) Partial lesion resolution 2 2.1 CASE REPORT Case 1 Female patient, 70 years old, leucoderma attended in at the Oral Medicine clinic in August 2016, complaining of burning and mouth sores for about 12 months. During the anamnesis, she reported using mouthwashes containing 100,000 IU nystatin (10 ml/4 times a day) and 0.05% clobetasol propionate (10 ml/3 times a day) as previous treatments, without success. Concerning her health history, the patient was a former smoker, hypertensive, with gastroesophageal reflux, gastritis, arthritis, osteoarthritis and osteophytosis, taking Enalapril (10 mg/day), Carvedilol (3.125 mg/2 times a day), Omeprazole (20 mg/day), calcium supplements (500 mg/400 IU/day) and vitamin D (7,000 IU/day). An intraoral physical examination indicated multiple bilateral erythematous macules on the buccal mucosa and palate, as well as a depapillary tongue (Figure 1A). A clinical hypothesis of oral candidosis and anemia was established and, after noting vitamin B12 dosage (56 pg/ml) and intrinsic factor autoantibody alterations, complementary exams were requested, and the patient was referred to a gastroenterologist to assess nutritional deficiency. Vitamin B12 was prescribed parenterally (1,000 μg /one time per week and once a month after 4 weeks) and the patient returned after 30 and 60 days, showing considerable symptom and clinical aspect improvements, but without total remission (Figure 1B). 2.2 Case 2 Female patient, 61 years old, leucoderma, attended at the Oral Medicine clinic of the same institution in April 2017, complaining of tongue burning, with 12 months of evolution, presenting remission and exacerbation periods. During the anamnesis, the patient reported being a former smoker, hypertensive, with arthritis, osteoarthritis and reflux gastroesophageal, taking Losartan (12.5 mg/day), Atenolol (100 mg/day), Diazepam (5 mg/day) and a calcium supplement (500 mg/400 IU/day), in addition to having already used prednisolone (20 mg/day), clonidine (0.100 m/day) and methotrexate (10 mg/week). As a previous treatment for oral symptoms, the patient reported having performed mouthwashes with a ginger solution, without no symptom resolving. An extraoral physical examination did not reveal any changes. During an intraoral physical examination, areas presenting slight depapillation and cracks in the dorsum and right and left lateral borders of the tongue were observed (Figure 2A). The initial diagnoses were burning mouth syndrome and geographic tongue. Additional tests were requested and serum vitamin B12 and B9 levels (<200 pg/ml) were below normal. The patient did not undergo a gastrectomy, so she was referred to a gastroenterologist to assess nutritional deficiency and received the same vitamin B12 supplementation protocol for (1,000 μg /two capsules a day for 60 days), which led to partial symptom improvement after 60 days (Figure 2B). 2.3 Case 3 Male patient, 47 years old, melanoderma, attended at the Oral Medicine clinic in November 2018, complaining of burning and tongue erythema, lasting 8 months. Concerning the current disease history, the patient reported having previously undergone treatment with Nystatin 100,000 IU (10 ml/4 times a day), hydrogen peroxide (1 tablespoon in 1/2 glass of water) and triamcinolone acetonide (1 mg/g/3 times a day), but without satisfactory results. Concerning FIGURE 2 resolution (A) Bilateral depapillated area in the posterior tongue region observed in the initial consultation. (B) Partial clinical F I G U R E 3 (A) Initial patient aspect, presenting an erythematous lesion on the ventral tongue area. (B) Full clinical resolution after vitamin supplementation medical history, the patient reported undergoing antibacterial treatment due to a Helicobacter pylori infection. An extraoral physical examination did not reveal any changes, while an intra-oral examination demonstrated the presence of erythematous macules in the buccal vestible, lateral border, ventral, and tongue dorsum (Figure 3A). Initially, oral erosive lichen planus was suspected, but after an incisional biopsy, this hypothesis was discarded and a probable vitamin B12 deficiency was suspected, which was later confirmed by a laboratory examination (B12 66 pg/ml). The patient was referred to a gastroenterologist to assess the origin of the nutritional deficiency and complete clinical improvement was observed following vitamin B12 supplementation after 60 days (1,000 μg/2 capsules per day, for 60 days). Currently, the patient is being followed up with no disease exacerbation signs and symptoms (Figure 3B). 2.4 Case 4 Female patient, 58 years old, melanoderma, attended at the Oral Medicine clinic in November 2019, complaining of tongue burning and erythema, lasting 24 months. During an anamnesis, no previous lesion treatment was reported. Concerning health history, the patient presents heart disease and gastritis, in addition to using benzopyronone 15 mg associated with troxerutin 90 mg 3 times a day. An extraoral physical examination did not reveal any changes, while an intraoral examination demonstrated the presence F I G U R E 4 (A) and (B) Initial clinical patient aspect, with presenting erythematous macules in the buccal vestible, lateral border, ventral side, and dorsum of the tongue. (C) and (D) Total lesion resolution of erythematous macules in the lower lip mucosa and tongue lateral borders, ventral area and apex (Figures 4A and 4B). A clinical suspicion of hypovitaminosis was confirmed by a laboratory exam (B12 168 pg/ml). Thus, the patient was referred to a gastroenterologist to assess the origin of the nutritional deficiency. Vitamin B12 was prescribed for 60 days (1,000 μg /two capsules per day) and the patient returned after 60 days, displaying complete lesion and symptom remission (Figures 4C and 4D). 3 DISCUSSION This article describes four cases of patients presenting vitamin B12 deficiency and brings important contributions concerning diagnoses, differential diagnoses and clinical conducts for patients presenting this condition in the dental clinic. Vitamin B12 is associated with proteins in several types of foods, such as milk, fortified cereals, eggs and meat. Upon reaching the acidic stomach environment, this vitamin is released due to pepsin digestion and immediately binds to haptocorrin or transcobalamin I, produced by the salivary glands with the function of protecting vitamin B12 from acidic degradation. However, for this vitamin to be absorbed, haptocorrin must be degraded and the vitamin must bind to a glycoprotein produced by gastric parietal cells, called the Intrinsic Factor, in order to form the intrinsic Factor-vitamin B12 complex (FI-B12), which binds to the cuban receptor responsible for mediating the uptake of this complex in the duodenum and ileum enterocytes, via endocytosis. This mechanism is responsible for most of ingested vitamin B12 absorption, although this may also take place through passive diffusion.6,7 Vitamin B12 is essential for neural function, red blood cell production and DNA synthesis, as well as a metabolic reaction co-factor.2 Its deficiency can result in megaloblastic anemia, which is indistinguishable from folate (vitamin B9) and iron deficiencies.8 Patients presenting this type of anemia exhibit slowly progressing symptoms, including weakness, fatigue, shortness of breath and neurological abnormalities.1