Version July 2025
INTRODUCTION —
AA (secondary) amyloidosis is a condition in which fragments of serum amyloid A protein (SAA) form fibrils that are deposited in extracellular tissue. This process is usually driven by inflammation, as SAA is an acute phase reactant. AA amyloidosis may complicate several chronic inflammatory conditions, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), autoinflammatory diseases, inflammatory bowel disease (IBD), chronic infections, and certain neoplasms (table 1) [1-3].
The treatment of AA amyloidosis is presented here. Other aspects of AA amyloidosis are described separately, including pathogenesis, causes, and diagnosis (see "AA amyloidosis: Pathogenesis" and "AA amyloidosis: Causes and diagnosis"). An overview of amyloidosis is also described elsewhere. (See "Overview of amyloidosis".)
PREVENTION OF AA AMYLOIDOSIS —
Since the pathogenesis of AA amyloidosis largely depends on inflammation related to another condition, control of the underlying condition should in theory reduce the risk of developing AA amyloidosis.
There has been a dramatic reduction in cases of AA amyloidosis after the introduction of more effective treatments for various inflammatory conditions, such as familial Mediterranean fever (FMF) or juvenile idiopathic arthritis (JIA) [4]. However, data are limited to support specific preventive strategies in patients who have conditions that increase their likelihood of developing AA amyloidosis. Examples of the impact of therapy on preventing amyloidosis include the following:
●FMF – Colchicine is commonly used for the prevention of AA amyloidosis in patients with FMF, which is the most common monogenic autoinflammatory disease worldwide and is associated with MEFV mutations; this is discussed in more detail elsewhere. FMF variants associated with AA amyloid are M694V (homozygous, heterozygous, and deletion mutant) and, to a lesser extent, (M680I not M690I). (See "Management of familial Mediterranean fever", section on 'Preventing AA amyloidosis'.)
●CAPS – Cryopyrin-associated periodic syndromes (CAPS) are monogenic autoinflammatory diseases related to NLRP3 mutations. The use of interleukin 1 (IL-1) inhibitors has resulted in a dramatic decrease in the occurrence of AA amyloidosis [5]. The risk of AA amyloidosis appears related to the severity and duration of the disease.
●Adult-onset Still's disease – The frequency of AA amyloidosis complicating adult-onset Still's disease has also decreased since the introduction of biologic therapies (eg, IL-1 and IL-6 inhibitors) [6].
TREATMENT OF AA AMYLOIDOSIS —
The primary goal of therapy of AA amyloidosis is control of the underlying inflammatory disease responsible for serum amyloid A protein (SAA) production. Patients with specific organ involvement (eg, kidney disease) may benefit from additional therapeutic approaches.
Treatments aimed at preventing SAA fibril formation or removing existing amyloid deposits are under active investigation but are not clinically available. (See 'Investigational approaches' below.)
Treatment of the underlying process — It is critical to treat the underlying process driving the production of SAA in patients with AA amyloidosis. Specific therapy depends upon the associated inflammatory disease, such as immunosuppression for inflammatory arthritis, antibiotics for chronic bacterial infections, and surgical resection or chemotherapy for malignancy.
The fibril precursor in AA amyloid, SAA, is a normal plasma protein that is produced by hepatocytes as part of the physiologic acute phase response. A chronic inflammatory state leads to sustained high levels of the acute phase proteins [7]. Successful treatment of the underlying inflammatory process reduces hepatic production of the acute phase response and therefore reduces circulating SAA to normal levels. Over time, this can lead to stable or improved kidney function, reduced urinary protein excretion, and partial resolution of amyloid deposits (as assessed by scintigraphy with radiolabeled serum amyloid P component [SAP], when available) [2,8-15].
Evidence to support the benefits of controlling underlying disease and subsequent inflammation comes primarily from uncontrolled series and cohort studies. As an example, a cohort study prospectively followed 80 patients with AA amyloidosis (mostly with rheumatoid arthritis [RA] or juvenile idiopathic arthritis [JIA]) for a median of four years and assessed systemic amyloid load yearly by SAP scintigraphy; all patients received aggressive treatment for their underlying condition [16]. Patients with median serum SAA levels within the reference range (<10 mg/L) had a higher estimated 10-year survival (90 versus 40 percent in those with higher median values); most of them had stabilization or regression of amyloid load, as well as stable or improving serum creatinine concentration and proteinuria in those with concurrent kidney involvement. Similar findings have been noted in other uncontrolled series in patients with various conditions, including RA, ankylosing spondylitis (AS), JIA, Crohn disease, and Castleman disease (angiofollicular lymph node hyperplasia) [9,10,13-15,17-19].
Autoinflammatory and immunoinflammatory diseases
Familial Mediterranean fever — AA amyloidosis may occur in patients with familial Mediterranean fever (FMF). The risk is increased when patients have two homozygous M694V MEFV mutations [20]. Rarely, patients with only one pathogenic MEFV variant may also develop AA amyloidosis [21,22].
The prevention and treatment of AA amyloidosis in patients with FMF are discussed in detail separately. (See "Management of familial Mediterranean fever", section on 'Preventing AA amyloidosis'.)
Other monogenic autoinflammatory diseases — AA amyloidosis can be seen in patients with other monogenic autoinflammatory diseases, including the following:
●Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), including variants in T50M, T79M and C70R [23] (see "Tumor necrosis factor receptor-1 associated periodic syndrome (TRAPS)", section on 'Management')
●Cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disorder (NOMID) [5] (see "Cryopyrin-associated periodic syndromes and related disorders", section on 'Treatment of cryopyrinopathies')
●Mevalonate kinase deficiency [24,25] (see "Hyperimmunoglobulin D syndrome: Management")
●Deficiency of adenosine deaminase 2 (ADA2), including variant Y453C [26,27] (see "Deficiency of adenosine deaminase 2 (DADA2)")
●Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome [28] (see "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome')
●Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome, including variant T237M [29] (see "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'ALPK1 gain-of-function defects (ROSAH syndrome)')
●Dedicator of cytokinesis 11 (DOCK11) deficiency [30]
●Proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) associated myeloid-related proteinemia inflammatory (PAMI) syndrome [31]
Treatment of these conditions, and data on prevention or treatment of related amyloidosis if available, is presented in the respective disease management topics.
Inflammatory arthritis — Many types of inflammatory arthritis have been associated with the development of AA amyloidosis, including RA, JIA, psoriatic arthritis (PsA), and AS. The treatment of AA amyloidosis in such patients focuses on the treatment of the underlying inflammatory arthritis.
Tocilizumab for most patients — For patients with AA amyloidosis related to a type of inflammatory arthritis for which tocilizumab is an approved therapy, we suggest using tocilizumab rather than alternative biologic disease-modifying antirheumatic drugs (bDMARDs) (Grade 2C). Examples include patients with RA and polyarticular and systemic JIA. By contrast, if patients have spondyloarthritis (eg, PsA, AS, inflammatory bowel disease [IBD]-related arthritis) where bDMARDS other than tocilizumab are generally used, we monitor serial SAA measurements on the standard therapy for that type of arthritis; if SAA levels remain persistently elevated, then we switch to tocilizumab. Of note, tocilizumab is associated with an increased risk of intestinal perforation, especially in the setting of diverticulosis, and should be used with caution in patients with gastrointestinal disease.
Tocilizumab is a humanized anti-interleukin 6 (IL-6) receptor antibody. It notably can be used in patients with some degree of kidney function impairment (adjustment is not needed for patients with a creatinine clearance of ≥30 mL/minute). The dosing, contraindications, and monitoring of tocilizumab in this setting are the same as when it is used to treat inflammatory arthritis without concomitant AA amyloidosis, which is described in detail elsewhere. (See "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'Tocilizumab' and "Interleukin 6 inhibitors: Biology, principles of use, and adverse effects".)
Direct evidence to support the use of tocilizumab over other immunosuppressive therapies is limited. In an observational study, 59 patients with renal AA amyloidosis related to chronic inflammatory diseases (34 patients, including 18 with RA) or unknown causes (25 patients) were followed for a mean of 4.8 years; 58 percent were treated with tocilizumab and 42 percent received other bDMARDs [32]. Compared with other bDMARDs, the use of tocilizumab was associated with a greater reduction in serum AA and a lower rate of progression to end-stage kidney disease (ESKD; 21 percent in patients taking tocilizumab versus 64 percent in patients taking other bDMARDs). In another retrospective review of 42 patients with RA and AA amyloidosis treated with tocilizumab or TNF antagonists, tocilizumab was more effective at normalizing SAA levels and improving estimated glomerular filtration rate (eGFR) [33].
With respect to the use of tocilizumab across various forms of inflammatory arthritis, multiple case reports and series support the use of tocilizumab in treating AA amyloidosis complicating RA [34-38], PsA [39-41], and JIA [42,43]. Tocilizumab has not been effective for treatment of AS alone but has reportedly been effective for treatment of AA amyloidosis in patients with AS [44]. Indirect evidence to support the use of tocilizumab in treating various forms of inflammatory arthritis is described in the respective disease topics.
Alternative therapies — Data to support the use of other antiinflammatory therapies in patients with AA amyloidosis and different subtypes of inflammatory arthritis are summarized below:
●RA
•The TNF inhibitors adalimumab, etanercept, and infliximab have been shown in case series to be effective in treating patients with RA and AA amyloidosis [45-49]. Less information is available regarding certolizumab pegol and golimumab. The effectiveness of the TNF antagonists appears to be directly related to their ability to control the underlying inflammatory disorder [50,51]. Regression of tissue amyloid may occur as early as three months, as documented by gastrointestinal biopsies in some instances [52].
A small study comparing the efficacy of cyclophosphamide versus etanercept in patients with RA and AA amyloidosis found improved survival, proteinuria, and eGFR in patients receiving etanercept [53].
•Janus kinase (JAK) inhibitors have also been proposed as a way to treat AA amyloidosis and RA. Tofacitinib, a JAK inhibitor that targets JAK1, has been shown to decrease SAA levels in patients with RA; however, patients with AA amyloidosis were not included in this study [54].
•Case reports and series have described the successful use of biologic agents without direct anticytokine activity, including abatacept [55] and rituximab [56], or treatment with a cytostatic agent such as cyclophosphamide [9,14,19].
More information about treating RA, including indirect evidence to support the use of the above agents, is provided separately:
•(See "General principles and overview of management of rheumatoid arthritis in adults".)
•(See "Initial treatment of rheumatoid arthritis in adults".)
•(See "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy".)
●PsA – Case series and reports have described the successful use of biologic agents for AA amyloidosis associated with PsA, including TNF inhibitors [45,46,57,58] and anti-IL-17 therapy (specifically, secukinumab) [57]. More information about treating PsA is provided separately. (See "Treatment of psoriatic arthritis".)
●AS – Multiple case series support the use of TNF inhibitors in treating AA amyloidosis associated with AS [45,46,48,59]. More information about treating AS is provided separately. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults".)
●JIA – Case reports and series have suggested benefit from treatment with TNF inhibitors [45,49]. In a longitudinal cohort study of patients with JIA and AA amyloidosis, the mortality rate was lower for patients who received conventional DMARDs and/or cytostatic agents (eg, cyclophosphamide) compared with patients taking glucocorticoid monotherapy [6,60]. More information on treating various types of JIA is provided separately:
•(See "Oligoarticular juvenile idiopathic arthritis", section on 'Treatment'.)
•(See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis".)
•(See "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)
•(See "Spondyloarthritis in children", section on 'Treatment of enthesitis related arthritis'.)
•(See "Systemic juvenile idiopathic arthritis: Treatment and prognosis".)
Chronic gout — Gout has rarely been associated with the development of AA amyloidosis [61-63]. For most patients with gout complicated by AA amyloidosis, we suggest using IL-1 inhibitors in addition to urate-lowering therapy, rather than alternative antiinflammatory medications. Therapy is given chronically, as is done for certain types of inflammatory arthritis (eg, RA), rather than episodically (as is sometimes done for gout that is not complicated by AA amyloidosis). The dosing, monitoring, and adverse effects of IL-1 inhibitors are discussed in detail separately. (See "Interleukin 1 inhibitors: Biology, principles of use, and adverse events".)
Our approach is based on case reports of IL-1 inhibitors being effective treatment for gout as well as AA amyloidosis [63] and the authors' clinical expertise. More information about the treatment of chronic gout, including the use of IL-1 inhibitors, is provided separately. (See "Gout: Treatment of flares", section on 'Interleukin 1 blockade' and "Gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
Inflammatory bowel disease — AA amyloidosis can very rarely complicate Crohn disease and ulcerative colitis [64]. Limited evidence suggests that the immunosuppressive therapies used to treat IBD are also beneficial for the treatment of AA amyloidosis, such as TNF inhibitors and JAK inhibitors. A retrospective study of 83 patients with renal AA amyloidosis who were taking bDMARDs, including eight patients with underlying IBD, noted improvement in serum AA and proteinuria over a mean period of 4.8 years [32]. In addition, a case report and case series found that infliximab and other TNF inhibitors may be effective in treating AA amyloidosis complicating Crohn disease [65,66]. While use of IL-6 inhibitors in patients with AA amyloidosis related to IBD has been reported [32], IL-6 inhibitors are not effective for the treatment of IBD [67] and have been associated with a risk of gastrointestinal perforation, and they should therefore be used with caution [68].
Other inflammatory conditions — Tocilizumab, a humanized anti-IL-6 receptor antibody, has been effectively used for AA amyloidosis complicating other inflammatory conditions including Behçet syndrome, Castleman disease (CD; angiofollicular lymph node hyperplasia), and Sweet syndrome [34-36,42,44,69]. Chronic colchicine therapy (0.6 mg twice daily) has been reported to be effective in patients with AA amyloid due to Behçet syndrome, mimicking the higher doses used to suppress amyloidogenesis in FMF compared with doses used for gout prophylaxis [70].
Castleman disease — AA amyloidosis has been associated with CD. The optimal treatment strategy depends on whether the disease is unicentric or multicentric.
●Multicentric CD (MCD) – In most patients with AA amyloidosis related to MCD, we suggest the use of tocilizumab rather than other types of immunosuppressive therapies. The approach to medication dosing and monitoring are described in detail elsewhere. (See 'Tocilizumab for most patients' above and "Interleukin 6 inhibitors: Biology, principles of use, and adverse effects".)
Direct evidence to support this approach is very limited. In a systematic literature review of case series and reports, 6 of 14 patients with AA amyloidosis related to MCD achieved complete remission on tocilizumab [71]; remission was not reported in any patient who was taking alternative immunosuppressive agents, including azathioprine, anti-CD20 agents, cyclophosphamide, or hematology-derived chemotherapy regimens. The treatment of patients with MCD without associated AA amyloidosis, including the use of tocilizumab, is described in detail elsewhere. (See "HHV-8-negative/idiopathic multicentric Castleman disease" and "HHV-8/KSHV-associated multicentric Castleman disease".)
●Unicentric CD – The treatment of AA amyloidosis related to unicentric CD is surgical resection, as is done for patients with unicentric CD who do not have amyloidosis (see "Unicentric Castleman disease", section on 'Treatment'). In case reports and case series of patients with systemic AA amyloidosis complicating unicentric CD, resection of the tumors may have led to clinical regression of the amyloid, which was also corroborated by SAP scintigraphy [12,71,72].
Chronic infection — Chronic infections such as osteomyelitis, bronchiectasis, tuberculosis, hepatitis C virus, and human immunodeficiency virus (HIV) may be associated with development of AA amyloidosis [73,74]. In such cases, patients require treatment of the underlying infection.
There is no role for the addition of systemic antiinflammatory therapy in patients with AA amyloidosis from chronic infection. A case report described the use of colchicine to treat amyloidosis in a patient who used injectable drugs and developed recurrent skin infections [75]. Proteinuria was almost completely resolved with therapy; however, a repeat kidney biopsy did not demonstrate a reduction in total amyloid deposition.
Malignancy — Various solid malignancies are associated with AA amyloidosis, most commonly renal cell carcinoma [76]. Hematologic neoplasms can be associated with histologically proven AA amyloidosis, including histiocytosis [77-81], hyperinflammatory lymphoma [82], and hyperinflammatory gammopathies such as Schnitzler syndrome, Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma [83,84].
Treatment should be targeted to the malignancy, such as surgical resection and/or chemotherapy. As an example, there have been case reports of AA amyloidosis caused by hepatic adenomas that secrete large amounts of IL-6; these were successfully treated with surgical resection of the adenoma [85].
Hereditary and idiopathic AA amyloidosis — In most patients with idiopathic AA amyloidosis, we suggest starting tocilizumab rather than alternative immunosuppressive agents. The approach to medication dosing and monitoring are described in detail elsewhere. (See 'Tocilizumab for most patients' above and "Interleukin 6 inhibitors: Biology, principles of use, and adverse effects".)
Treatment with biologic agents may be effective for patients with hereditary and idiopathic AA amyloidosis [32]. Tocilizumab was shown to be beneficial for AA amyloidosis in a family with the SAA1.1 haplotype linked to a polymorphism in the SAA promoter [86]. In a small cohort study of 11 patients with idiopathic AA amyloidosis who were treated with the IL-1 receptor antagonist anakinra, nine patients responded with significant reductions in SAA [87].
Other conditions — Common variable immunodeficiency can be complicated by AA amyloidosis [88]. Patients with frequent infections related to common variable immunodeficiency may also benefit from immunoglobulin replacement [88]. (See "Treatment and prognosis of common variable immunodeficiency", section on 'Immune globulin replacement therapy'.)
Cases of AA amyloidosis without an etiology other than obesity have been described [89-91], which may be related to the synthesis of SAA in adipocytes [92]. Controlling weight should theoretically help control disease in such patients, but there are no data to support this approach. More information on specific weight-loss strategies is provided elsewhere. (See "Obesity in adults: Overview of management".)
Organ-specific manifestations — There are a variety of other organ-specific manifestations in AA amyloidosis [3]. A more detailed discussion of the treatment of AA amyloidosis affecting specific organ systems is covered in the following topics:
●Kidney manifestations, such as proteinuria and chronic kidney disease (see "Renal amyloidosis", section on 'Supportive measures in all patients')
●Gastrointestinal manifestations (approximately 30 percent), such as bleeding, malabsorption, protein-losing enteropathy, or dysmotility (see "Gastrointestinal amyloidosis: Clinical manifestations, diagnosis, and management", section on 'Management')
●Cardiac manifestations, such as atrial fibrillation and conduction system disease (see "Cardiac amyloidosis: Treatment and prognosis", section on 'General management')
AA amyloidosis may also rarely be complicated by thyroid goiter, which has been described in patients with FMF who have ESKD related to amyloidosis [93]. Thyroidectomy may be required for diagnosis and/or to treat compressive symptoms. (See "Clinical presentation and evaluation of goiter in adults" and "Treatment of benign obstructive or substernal goiter".)
Investigational approaches — Various therapeutic approaches for AA amyloidosis have been proposed that could either prevent fibril formation and subsequent deposition or reduce existing amyloid deposits. An overview of investigational strategies in amyloidosis is provided elsewhere. (See "Overview of amyloidosis", section on 'Other approaches and investigational strategies'.)
Examples of strategies tested in patients with AA amyloidosis include the following:
●Binding to cofactors and peptidic inhibitors – One investigational approach involves using cofactors or peptidic inhibitors to interfere with fibril formation [94-96]. The efficacy and safety of one such inhibitor, eprosidate, were evaluated in a randomized trial in patients with AA amyloidosis and kidney involvement, which found that eprosidate reduced the risk of worsening kidney disease compared with placebo [97]. However, drug development was terminated after a second international phase 3 randomized trial (NCT012157470) failed to confirm benefit. Other cofactors and peptidic inhibitors are being investigated.
●Clearance of amyloid deposits from tissue – Another investigational approach involves the use of immunotherapy to promote the clearance of existing amyloid deposits. The target of the immunotherapy could be SAA or other non-fibrillar components that are found in all types of amyloid, such as SAP.
Monoclonal anti-AA antibodies have been developed for the in vivo imaging of AA amyloidosis and potential mobilization of amyloid deposits from tissue [98], but extended efficacy remains to be established. An anti-AA antibody directed to an epitope derived from an SAA cleavage site was also found to recognize a cryptic epitope shared with human light chain (AL) amyloid [99].
Antibodies targeting SAP hold promise for treating various types of amyloidosis. In particular, a phase 1 trial testing the combination of a bis (proline) compound (CPHPC) and anti-SAP antibodies showed clearance of amyloid deposits in various organs; it included one patient with AA amyloidosis. This approach is discussed in more detail elsewhere. (See "Overview of amyloidosis", section on 'Other approaches and investigational strategies'.)
PROGNOSIS —
If untreated, AA amyloidosis is a serious disease with significant mortality due to end-stage kidney disease (ESKD), infection, heart failure, bowel perforation, and/or gastrointestinal bleeding [8,100,101]. Patients with persistently high circulating levels of serum amyloid A protein (SAA) are at particular risk of these complications [102,103]. As an example, in a review of 374 patients with AA amyloidosis, the median survival from diagnosis was 133 months [8]. Poor prognostic factors included older age, lower serum albumin levels, ESKD at baseline, and higher SAA elevation during follow-up [104].
Survival rates for patients with AA amyloidosis have progressively improved over time, which likely reflects earlier detection as well as improved treatment options for associated inflammatory disorders [2,4,8,105].
Similarly, outcomes have improved over time for patients with ESKD due to AA amyloidosis who undergo kidney transplant, especially when biologic therapy is available to treat the underlying inflammatory condition [106,107]. In an observational study of 86 patients with AA amyloidosis who required kidney transplantation, the five-year survival rate was 86 percent, and only 6 percent of patients had a recurrence of renal amyloidosis [106]. The risk of recurrence of renal amyloidosis may be higher in patients with persistent SAA elevations; in another review of 48 patients with AA amyloidosis who underwent kidney transplantation, the recurrence rate was three times higher in patients with persistent SAA elevations posttransplant compared with patients with the lowest mean SAA levels [108]. More information on the outcomes of renal amyloidosis is described separately. (See "Renal amyloidosis", section on 'Outcomes in AA amyloidosis'.)
SUMMARY AND RECOMMENDATIONS
●Overview – AA (secondary) amyloidosis is a condition in which fragments of serum amyloid A protein (SAA) form fibrils that are deposited in extracellular tissue. This process is usually driven by inflammation, as SAA is an acute phase reactant. AA amyloidosis may complicate several chronic inflammatory conditions (table 1). (See 'Introduction' above.)
●Prevention of AA amyloidosis – Since the pathogenesis of AA amyloidosis largely depends on inflammation related to another condition, control of the underlying condition should in theory reduce the risk of developing AA amyloidosis. There has been a dramatic reduction in cases of AA amyloidosis after the introduction of more effective treatments for various inflammatory conditions. (See 'Prevention of AA amyloidosis' above.)
●Treatment of the underlying process – The primary goal of therapy is control of the underlying inflammatory disease responsible for SAA production; therefore, the optimal treatment will vary depending on the associated inflammatory disease (eg, immunosuppression for inflammatory arthritis, antibiotics for chronic bacterial infections, and surgical resection or chemotherapy for malignancy). Treatments to prevent SAA fibril formation or remove existing amyloid deposits are under active investigation but are not clinically available. (See 'Treatment of AA amyloidosis' above and 'Treatment of the underlying process' above.)
•Autoinflammatory and immunoinflammatory diseases
-Familial Mediterranean fever (FMF) – AA amyloidosis may occur in patients with FMF; the prevention and treatment of AA amyloidosis in these patients is discussed in detail separately. (See "Management of familial Mediterranean fever", section on 'Preventing AA amyloidosis'.)
-Inflammatory arthritis – For most patients with inflammatory arthritis complicated by AA amyloidosis, we suggest using tocilizumab rather than alternative biologic disease-modifying antirheumatic drugs (bDMARDs) (Grade 2C). If patients have a type of arthritis that is not typically treated by tocilizumab (eg, psoriatic arthritis [PsA], ankylosing spondylitis [AS], inflammatory bowel disease [IBD]-related arthritis), then we monitor serial SAA measurements on the standard therapies for that type of arthritis and switch to tocilizumab if SAA levels remain persistently elevated. (See 'Inflammatory arthritis' above.)
-Chronic gout – In most patients with gout complicated by AA amyloidosis, we suggest using interleukin 1 (IL-1) inhibitors in addition to urate-lowering therapy, rather than alternative antiinflammatory medications (Grade 2C). (See 'Chronic gout' above.)
-Inflammatory bowel disease (IBD) – Limited evidence suggests that the immunosuppressive therapies used to treat IBD are also beneficial for the treatment of AA amyloidosis, such as tumor necrosis factor (TNF) inhibitors and janus kinase (JAK) inhibitors. (See 'Inflammatory bowel disease' above.)
-Castleman disease (CD) – The optimal treatment strategy for AA amyloidosis associated with CD (angiofollicular lymph node hyperplasia) depends on whether the disease is unicentric or multicentric. In most patients with AA amyloidosis related to multicentric CD (MCD), we suggest the use of tocilizumab rather than other types of immunosuppressive therapies (Grade 2C). The treatment of AA amyloidosis related to unicentric CD is surgical resection, which prevents further amyloid deposition. (See 'Castleman disease' above.)
•Chronic infection and malignancy – Treatment of patients with AA amyloidosis related to infection or malignancy will vary depending on the underlying issue (eg, antibiotics for osteomyelitis, chemotherapy or surgical resection for malignancy). There is no role for the addition of systemic antiinflammatory therapy. (See 'Chronic infection' above and 'Malignancy' above.)
•Hereditary and idiopathic AA amyloidosis – In most patients with idiopathic AA amyloidosis, we suggest starting tocilizumab rather than alternative immunosuppressive agents (Grade 2C). (See 'Hereditary and idiopathic AA amyloidosis' above.)
●Treatment of organ-specific manifestations – More information about the treatment of AA amyloidosis affecting specific organ systems is provided separately. (See "Renal amyloidosis" and "Gastrointestinal amyloidosis: Clinical manifestations, diagnosis, and management" and "Cardiac amyloidosis: Treatment and prognosis".)
●Prognosis – If untreated, AA amyloidosis is a serious disease with significant mortality due to end-stage kidney disease (ESKD), infection, heart failure, bowel perforation, and/or gastrointestinal bleeding. Survival rates for patients with AA amyloidosis have progressively improved over time, likely reflecting earlier detection and improved treatment options for associated inflammatory disorders. (See 'Prognosis' above.)
