Profile of Biermer’s Disease at the Medical Clinic II Abass Ndao Hospital Center: About 57 Colliged Cases

Introduction: Biermer’s disease is an autoimmune cause of anemia characterized by malabsorption of vitamin B12. It is often accompanied by other autoimmune pathologies. The objective was to study its profile in patients followed in the internal medicine department of the Abass Ndao hospital center. Methods: This was a retrospective and descriptive study of patients followed for Biermer’s disease from January 1, 2014 to December 31, 2019 (5 years). Results: 57 cases were collected, an incidence of 5.4 in the internal medicine department. The sex ratio was 0.58, an average age of 56.4 years. The cir-cumstances of discovery were dominated by anemic syndrome (87.7%), dermatological (33.3%), digestive (29.8%), neurological (20%) pathologies. The specific signs to Biermer’s disease were digestive manifestations in 70.2% (in-cluding 30% Hunter’s glossitis), neurological manifestations in 36.8% posed on the data in the literature. His prognosis under treatment is good whatever the route of administration of vitamin B12.


Introduction
Biermer's disease (formerly known as pernicious anemia) is an autoimmune atrophic gastritis, predominantly fundic, responsible for a malabsorption of vitamin B12. It is characterized immunologically by the presence of anti-intrinsic factor antibodies and/or anti-parietal cells antibodies. Its prevalence is 0.1% in the general population and 1.9% in subjects over 60 years of age. It accounts for 50% of the etiologies of vitamin B12 deficiency in adults [1]. It most often manifests as a neuro-anemic syndrome associated with digestive signs, notably Hunter's glossitis and melanoderma. It is often associated with other autoimmune disorders (vitiligo, dysthyroidism, autoimmune adrenal insufficiency, Sjögren syndrome) [2] [3]. Its treatment is based on the administration of vitamin B12 for life by the parenteral route [1] or oral [4]. Biermer's disease remains insufficiently described in Senegal. In Senegal, an old retrospective study carried out in 2008 focused on this pathology but did not assess the impact of oral treatment.
The objective of this study will be therefore to study the clinical epidemiological profiles but also the associated comorbidities and the course of treatment in patients followed at the Abass Ndao Hospital Center.

Patients and Methods
This was a retrospective, descriptive study of the cases of Biermer's disease collected over a period of 05 years (from January 1, 2014 to December 31, 2019).
We included in the study any patient for whom the diagnosis of Biermer's disease was confirmed. Apart from clinical manifestations, the confirmation of Biermer's disease in our series was carried out on a bundle of arguments. These were: the existence of a macrocytic type anemia (mean corpuscular volume > 100 fl) and/or a decrease in serum vitamin B12 levels (vitamin B12 less than 130 ng/l) and/or megaloblastosis in the medullogram and/or a positivity of intrinsic anti-factor antibodies and/or the presence of endoscopic or histological signs of atrophic gastritis. Incomplete records (hemogram, serum vitamin B12, anti-intrinsic factor antibody, esogastroduodenal fibroscopy, medullogram) were not included. The data were collected on a pre-established survey sheet and were also collected from patient medical records. The parameters necessary for the study were: • Socio-demographic data: age, sex, existence of an associated autoimmune disease; We also took into account the biological data: hemogram, myelogram, serum The adjuvant treatments were an iso-group iso-rhesus blood transfusion in case of poorly tolerated anemia, iron supplementation for iron deficiency, eradicator treatment for Helicobacter pylori.
The evolution under treatment was evaluated on the erythrocyte response after 7 days of treatment (the erythrocyte crisis was retained on an increase in the reticulocyte level greater than 10 times normal), on the correction of anemia over 3 months, the state of neurological, gastric manifestations and death.
The results were captured and analyzed using an electronic questionnaire developed with SPSS 24.0 software. This software was used to calculate frequencies, averages and standard deviations.

Epidemiological Data
We included 57 patients among 1044 patients followed in internal medicine (consultation and hospitalization) during the study period, an incidence of 5.46%.
These were 21 men and 36 women, for a sex ratio of 0.58. The average age of the patients was 54.6 ± 13 years (extremes of 27 and 80 years). It was on average 53 years for women and 59.2 years for men ( Table 1). The most represented age group for women was 40 -60 years old (61.1%) and that of men over 60 years old (47.6%). Figure 1 shows the distribution of age groups by gender.

Clinical Data
The average delay of consultation was 15 months. The reasons for consultation were dominated by symptoms of anemia in 87.7%, followed by dermatological Open Journal of Internal Medicine

Paraclinical Data
The hemogram found anemia in 93% of patients (n = 53). The average hemoglobin level was 6.8 g/dl (extremes of 1.8 and 15). It was less than 5 g/dl in 33.3% and between 5 and 8 g/dl in 24.6%. The mean corpuscular volume (MCV) was Open Journal of Internal Medicine   Helicobacter Pylori was found in 3.5% of cases (n = 2).

Discussion
It was a retrospective, descriptive study of the profile of Biermer's disease. It presented limits because the paraclinical explorations, often necessary for the diagnosis, were not always accessible. The exploration prices were on average 87,000 fcfa for vitamin B12 + antibodies against intrinsic factors, 12,000 fcfa for the medullogram and 30,000 fcfa for digestive endoscopy. As a result, many patients did not carry out all of the necessary investigations.

Epidemiological Data
The female prevalence and the average age noted in our series were superimposable on the data of the literature [5] [6] and comparable to the gender profile of autoimmune diseases. Biermer's disease is described as rare before 30 years of age, with a frequency which then increases, reaching a peak around 60 years of age [7]. The average delay of consultation was 15 months. This long delay is partly linked to the chronic and asymptomatic nature of the disease.

Clinical Data
Anemia is almost constant during Biermer's disease and is the main manifestation reported in Sub-Saharan Africa [5] [6]. In the series by Ndiaye et al. [6], the revealing manifestations were dominated by anemia in 100% of the cases, fol- Biermer's disease [8]. Furthermore, the combined degeneration of the spinal cord remains the classic neurological picture during this disease. According to Ndiaye et al. [6], it represents 20% to 30% of Biermer's diseases with neurological presentation. We found 10% of combined sclerosis of the spinal cord. Palmoplantar melanoderma found in 68.4% of our patients remains less described in the literature. It is more frequent in black subjects than in leukoderms [6]. The study by Ndiaye et al. [6] reported 42.3% of cases.

Paraclinical Data
On the biological level, the anemia found in 93%, remains frequently reported [7] [8] [9]. However, Biermer's disease can present without anemia [6]. In the series of Lindenbaum et al. [10] and Federici et al. [3], the hemoglobin level was normal in 24% and 28% respectively. Analysis of hematimetric constants noted macrocytosis more frequently (77%). Conventionally, Biermer's disease manifests with macrocytosis [6] [7] [11]. However, the mean corpuscular volume can also be normal in the case of Biermer's disease even in the absence of associated pathology [12]. Achlorydria can be the essential determinant through an associated iron deficiency. Besides anemia, leukopenia or thrombocytopenia are sometimes seen during this disease. In the Maktouf et al. [13] [8]. The positivity of anti-intrinsic factor antibodies remains specific at 98%. These antibodies can however be found in 2 to 5% of healthy subjects, as well as in 1st grade parents of an affected subject. [15]. However, the absence of anti-intrinsic factor antibodies and anti-parietal cell gastric antibodies does not rule out this diagnosis, since these immunological abnormalities are absent in approximately 30% of cases during authentic Biermer disease [16].
Histologically, the rate of atrophic gastritis found at 69% agrees with the literature [6] [14]. It is an almost constant diagnostic criterion reported with a high frequency in the majority of published studies. However, Biermer anemia can be observed outside of any gastric atrophy [5] [6]. A triggering role for Helicobacter pylori in the autoimmune process has been suggested [17].

Therapeutic Data
The parenteral route remains the preference in all African series [9] [12] [14].
However, recent studies have opened several perspectives by suggesting the in-Open Journal of Internal Medicine terest of the oral route or even the nasal route [4] [18]. There is no consensus on the dosage and timing of vitamin B12 during Biermer's disease. The same is true for the use of oral vitamin therapy. Many comparative therapeutic trials have confirmed the efficacy of vitamin B12 administered orally, in particular with the studies of Troilo et al. [19] and Kaltenbach et al. [20]. In fact, the first team to evaluate the effectiveness of vitamin B12 by the oral route, in Biermer's disease and para biermerian, noted a significant increase in the serum concentration of vitamin B12 on average by 161.6 ± 79 pg/ml in the maldigestion group (p < 0.00005) and 136.7 ± 67.4 pg/ml in the group of patients with Biermer's disease (p < 0.0001) [20]. Symptomatic treatment was mainly iso-rhesus iso-group blood transfusion in 61.4%. This rate was almost similar to that of Wun Chan et al. [8] which reported 76%.
The evolution marked by an improvement in the anemic syndrome and neurological signs was matching with the data in the literature [21] [22]. In the Andrès et al. [23] series, the average hemoglobin level increased from 6.2 to 12.4 g/l and the mean corpuscular volume from 103.5 to 91.2 fl in 4 months.
In our study, we observed an association with other autoimmune diseases in 12 patients. In the Tunisian studies of Maktouf et al. [8] and Achat et al. [24], it was found that mainly autoimmune thyropathies are in 23.4% and 57% respectively.

Conclusion
In Biermer's disease, the majority profile of the elderly female subject remains demonstrated. There is a clinical polymorphism dominated by anemia, Hunter's glossitis. The macrocytic profile dominates, however some chronic cases were revealed by normocytosis. The positive immunological assessment in our patients confirms our diagnoses. Upper gastrointestinal endoscopy remains crucial in the identification of atrophic gastritis. Because of its autoimmune nature, a systematic search for another associated autoimmune pathology is required.
Therapeutically, all our patients have benefited from lifelong B12 vitamin therapy mainly via the intramuscular route. At the end of this study, it would be important to evoke Biermer's disease before any macrocytosis, even isolated, in order to reduce the diagnostic delay, to use the alternative route to injectable treatment which is also effective, to make additional examinations accessible including immunological examinations for early diagnosis.