Evaluation of the Biochemical Subtypes of Amyloidosis without Immunohistochemistry according to the Recommendations of the International Amyloidosis Nomenclature Committee: A Multicenter Study in Dakar Involving 41 Cases
Introduction: Amyloidoses are a heterogeneous group of diseases characterized by extracellular deposits of insoluble fibrillar proteins in tissues. In sub-Saharan Africa, the epidemiology remains poorly understood, and the diagnosis of biochemical subtypes remains challenging in our clinical setting. The objective of our study was to determine the biochemical subtypes based on observed phenotypes, in accordance with international recommendations. Methods: This is a multicenter study combining a retrospective clinical review of hospital archives and an aggregation of cases documented in the scientific literature. All cases of histologically confirmed amyloidosis in patients over 16 years of age from January 1990 to October 2024 within level-3 national centers in Dakar were screened. Subtypes were systematically stratified into Confirmed (via immunohistochemistry/immunofluorescence), Probable (via predictive clinical phénotype and etiology guidelines), or Indeterminate categories. Results: A total of 41 cases were identified, including 18 men and 23 women (male-to-female ratio 0.78). The mean age was 59.93 ± 14.89 years. Regarding data sources, 36 cases (87.80%) were compiled from direct hospital archives and 5 cases (12.20%) were integrated from peer-reviewed publications. The most common manifestations were renal (75.61%, n = 31), cardiac (48.78%, n = 20), and gastrointestinal (39.02%, n = 16). The histological diagnosis was established via renal biopsy in 22 patients (53.65%), salivary gland biopsy in 13 patients (31.70%), skin biopsy in two patients (4.87%), bronchial biopsy in one patient (2.44%), and combined salivary-subcutaneous adipose tissue biopsy in three patients (7.31%). Definitive subtyping was Confirmed in only 3 cases (2 cases of AL and 1 case of AA). Based on phenotypes according to international guidelines, the remaining cases were classified as Probable AA in 20 patients, Probable AL in 12 patients, Probable senile ATTR in 2 patients, Probable beta-2-microglobulin in 2 patients, and Indeterminate in 2 patients. Sensitivity analysis excluding literature cases demonstrated no significant shift in subtype distribution. Chronic infectious or inflammatory etiologies underlaid all 21 AA cases, with tuberculosis alone accounting for 17.07% (n = 7) of the entire cohort. All AL amyloidosis cases were secondary to multiple myeloma. The 36-month survival rate was 60%, with age being the only factor statistically associated with death (p = 0.023). Conclusion: The incidence of amyloidosis in our region has been steadily
References
[1]
Merlini, G. and Bellotti, V. (2003) Molecular Mechanisms of Amyloidosis. NewEnglandJournalofMedicine, 349, 583-596. https://doi.org/10.1056/nejmra023144
[2]
Gertz, M.A. and Kyle, R.A. (1991) Secondary Systemic Amyloidosis: Response and Survival in 64 Patients. Medicine, 70, 246-256. https://doi.org/10.1097/00005792-199107000-00002
[3]
Buxbaum, J.N., Dispenzieri, A., Eisenberg, D.S., F?ndrich, M., Merlini, G., Saraiva, M.J.M., et al. (2022) Amyloid Nomenclature 2022: Update, Novel Proteins, and Recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid, 29, 213-219. https://doi.org/10.1080/13506129.2022.2147636
[4]
Nuvolone, M. and Merlini, G. (2017) Systemic Amyloidosis: Novel Therapies and Role of Biomarkers. NephrologyDialysisTransplantation, 32, 770-780. https://doi.org/10.1093/ndt/gfw305
[5]
Stankovic, K. and Grateau, G. (2008) AA Amyloidosis. Néphrologie&Thérapeutique, 4, 281-287. https://doi.org/10.1016/j.nephro.2008.02.002
[6]
Jaccard, A., Desport, E., Mohty, D. and Bridoux, F. (2015) AL Amyloidosis. LaRevuedeMédecineInterne, 36, 89-97. https://doi.org/10.1016/j.revmed.2014.08.003
[7]
Koumou, G.C.G., Sinomono, D.T.E., Merzouk, S., Kabbali, N., Harmouch, T., Arrayhani, M., et al. (2019) Renal Amyloidosis in Nephrology. PanAfricanMedicalJournal, 34, Article 79. https://doi.org/10.11604/pamj.2019.34.79.8722
[8]
Grateau, G., Valleix, S. and Callard, P. (2007) Multisystemic Amyloidosis in 2007. LaRevuedeMédecineInterne, 28, 281-283. https://doi.org/10.1016/j.revmed.2007.01.005
[9]
Bziz, A., Rouas, L., Lamalmi, N., Malihy, A., Cherradi, N., Ouzeddoun, N., et al. (2015) AA Renal Amyloidosis: Anatomopathological and Clinical Correlations in a Moroccan Series of 30 Cases. Néphrologie&Thérapeutique, 11, 543-550. https://doi.org/10.1016/j.nephro.2015.06.007
[10]
Diallo, S., Diouf, B., Ka, F., Niang, A., Pouye, A., Leye, A., et al. (2008) AL Amyloidosis in Black Patients: A Report on 4 Cases from Senegal. Médecined’Afrique Noire, 55, 471-477.
[11]
Muchtar, E., Dispenzieri, A., Magen, H., Grogan, M., Buadi, F., Lacy, M.Q., et al. (2021) Systemic Amyloidosis from AL to ATTR: General Review on Contemporary Diagnostic Methods. Blood, 137, 2933-2941.
[12]
Fatihi, E., Zahiri, K., Hachim, K., Fadel, H., Benghanem, G.M., Sqalli, S., et al. (1999) Value of the Biopsy of Accessory Salivary Glands in Amyloidosis. LaRevuedeMédecineInterne, 20, 759-761. https://doi.org/10.1016/s0248-8663(00)88681-6
[13]
Baudin, B. (2013) Biochemical Markers of the Nephrotic Syndrome. RevueFrancophonedesLaboratoires, 2013, 51-56. https://doi.org/10.1016/s1773-035x(13)72179-8
[14]
Isabel, C., Georgin-Lavialle, S., Aouba, A., Delarue, R., Nochy, D., Karras, A., et al. (2013) Cardiac Amyloidosis: A Series of 14 Patients, Description, and Prognostic Factors. LaRevuedeMédecineInterne, 34, 671-678. https://doi.org/10.1016/j.revmed.2013.05.003
[15]
Georgin-Lavialle, S. and Grateau, G. (2024) Clinical Aspects of Systemic Amyloidosis in 2024. Annales de Pathologie, 44, 407-413. https://doi.org/10.1016/j.annpat.2024.09.015
[16]
Quock, T.P., Yan, T., Chang, E., Guthrie, S. and Broder, M.S. (2018) Epidemiology of AL Amyloidosis: A Real-World Study Using US Claims Data. Blood Advances, 2, 1046-1053. https://doi.org/10.1182/bloodadvances.2018016402
[17]
Saba, M., Tohmé, A., Abadjian, G., Haddad, F. and Ghayad, E. (2005) Multisystemic Amyloidosis: Clinical Study of 39 Patients in Lebanon. La Presse Médicale, 34, 640-646. https://doi.org/10.1016/s0755-4982(05)84002-3
[18]
Ma?z, H.B., Moussa, F.B., Kaaroud, H., Abderrahim, E., Goucha, R., Abdallah, T.B., et al. (2001) Renal Amyloidosis: A Study of 420 Cases. The Journal of Internal Medicine, 249, Article 21.
[19]
Chugh, K.S., Datta, B.N., Singhal, P.C., Jain, S.K., Sakhuja, V. and Dash, S.C. (1981) Pattern of Renal Amyloidosis in Indian Patients. Postgraduate Medical Journal, 57, 31-35. https://doi.org/10.1136/pgmj.57.663.31
[20]
Fonseca, E.O. da, Filho, P.J.S., Silva, L.E. da and Caldas, M.L.R. (2015) Epidemiological, Clinical, and Laboratory Profile of Renal Amyloidosis: A 12-Year Retrospective Study of 37 Cases. Journal of Nephropathology, 4, 7-12.
[21]
Cazalets, C., Cador, B., Mauduit, N., Decaux, O., Ramée, M.-P., Le Pogamp, P., et al. (2003) Descriptive Epidemiology of Amyloidosis Cases Diagnosed at Rennes University Hospital from 1995 to 1999. LaRevuedeMédecineInterne, 24, 424-430. https://doi.org/10.1016/s0248-8663(03)00136-x
[22]
Villesuzanne, C. (2018) Epidemiological and Clinical Evolution of Immunoglobulin Light Chain (AL) Amyloidosis. Ph.D. Thesis, Université de Limoges.
[23]
Abdelghani, K.B., Barbouch, S., Ounissi, M., Mahfoudhi, M., Moussa, F.B., Goucha, R., et al. (2012) Etiological Profile of Amyloidosis in Tunisia among the Elderly. La TunisieMédicale, 90, 431-436.
[24]
Lachmann, H.J., Gillmore, J.D., Wechalekar, A.D., Gibbs, S.D., Pinney, J.H., Rowczenio, D.M., et al. (2012) THU0379 a 20 Year Single Centre Experience of Aa Amyloidosis Demonstrating Changes in Its Epidemiology. AnnalsoftheRheumaticDiseases, 71, 283-284. https://doi.org/10.1136/annrheumdis-2012-eular.2344
[25]
Lane, T., Loeffler, J.M., Rowczenio, D.M., Gilbertson, J.A., Bybee, A., Russell, T.L., et al. (2013) Brief Report: AA Amyloidosis Complicating the Hereditary Periodic Fever Syndromes. Arthritis&Rheumatism, 65, 1116-1121. https://doi.org/10.1002/art.37827
[26]
Papa, R. and Lachmann, H.J. (2022) Secondary, Inflammatory AA Amyloidosis: International Update and Diagnostic Management. Frontiers in Immunology, 13, Article No. 904351.
[27]
Tuglular, S., Yalcinkaya, F., Paydas, S., Oner, A., Utas, C., Bozfakioglu, S., et al. (2002) A Retrospective Analysis for Aetiology and Clinical Findings of 287 Secondary Amyloidosis Cases in Türkiye. NephrologyDialysisTransplantation, 17, 2003-2005. https://doi.org/10.1093/ndt/17.11.2003
[28]
Kyle, R.A., Larson, D.R., Kurtin, P.J., Kumar, S., Cerhan, J.R., Therneau, T.M., et al. (2019) Incidence of AL Amyloidosis in Olmsted County, Minnesota, 1990 through 2015. Mayo Clinic Proceedings, 94, 465-471. https://doi.org/10.1016/j.mayocp.2018.08.041
[29]
Genga, E., Oyoo, O. and Adebajo, A. (2018) Vasculitis in Africa. Current Rheumatology Reports, 20, Article No. 4. https://doi.org/10.1007/s11926-018-0711-y