**2. AA amyloidosis**

The precursor protein of the fibrils in AA amyloidosis is an apolipoprotein, called serum amyloid A, and produced in the liver in response to proinflammatory cytokines. AA amyloidosis, constituting up to 45% of all systemic amyloidosis cases, is associated with wide variety of chronic inflammatory conditions [5–7], summarized in the **Table 2**.


*LPD, lymphoproliferative disorders; CNS, central nervous system; PNS, peripheral nervous system; ANS, autonomous nervous system.*

#### **Table 1.**

*Amyloidoses with renal involvement.*

Kidneys are the main site of involvement in AA amyloidosis, renal damage (**Figure 1**) occurs in 90% of cases, presenting with proteinuria, nephrotic syndrome (NS) and impaired kidney function [3, 6].

Rheumatoid arthritis, if poorly controlled, still remains one of the most common inflammatory diseases, associated with AA amyloidosis (**Figure 2**).

However, many other conditions, listed in **Table 2**, may be causative for AA amyloidosis. Frequency of the diseases, associated with AA amyloidosis in the patients, followed in our unit, is shown in **Table 3**.

Worthy to note, that beyond traditional causes, several rare conditions, such as sarcoidosis, cystic fibrosis and Castleman's disease, complicated by AA amyloidosis, might be seen in the real practice (**Figures 3** and **4**).

Moreover, we recently described a patient with sclerosing angiomatoid nodular transformation of the spleen and AA amyloidosis [8], association previously unreported (**Figures 5** and **6**).

Presence of NS or proteinuria in patients with the history of any kind of chronic inflammatory conditions, indicates a high "suspicion index' with AA amyloidosis. The diagnosis demands pathology confirmation with kidney biopsy, demonstrating not only positive Congo red staining of the material, infiltrating kidney tissue (see **Figure 1**), but also apple-green birefringence in polarized light (**Figure 7**) and serum amyloid A expression (**Figure 8**).

Treatment goal in patients with AA amyloidosis is a complete control of the inflammatory process [6]. Due to the various characters of the underlying diseases, treatment may include surgery, antibiotics, anti-TNF agents, colchicine and several novel drugs. Kidney transplantation for the patients with the end stage of renal disease (ESRD) is an important option and may be considered if a stable control of the underlying disease has been achieved.

**79**

**Table 2.**

*Renal Amyloidosis*

**inflammation**

• Cystic fibrosis • Epidermolysis bullosa

• Paraplegia • Jejunoileal bypass • Intravenous drugs use

*DOI: http://dx.doi.org/10.5772/intechopen.81677*

**Chronic non-infectious diseases with persistent** 

**inflammation**

• Rheumatoid arthritis • Ankylosing spondylitis • Adult Still disease

• Psoriatic arthritis

*Bowel diseases* • Crohn's disease • Ulcerative colitis *Systemic vasculitis* • Behcet's disease • Polyarteritis nodosa • Giant cell vasculitis • Takayasu's arteritis • Polymyalgia rheumatica

*Other diseases* • Sarcoidosis • SAPHO syndrome • Schnitzler syndrome • Rosai-Dorfman disease

*Classic*

*Rare* • TRAPS

*HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome; SAPHO, synovitis, acne, pustules, hyperostosis, osteitis; TRAPS, TNF receptor associated periodic syndrome; NOMID, neonatal multisystem* 

*inflammatory disease; CINCA, chronic infantile neurological cutaneous and articular syndrome.*

• Recurrent idiopathic pericarditis

• Familial Mediterranean fever

• Muckle-Wells syndrome • NOMID/CINCA syndrome • Hyper-IgD syndrome

**Hereditary autoinflammatory syndromes**

• Other monogenic autoinflammatory syndromes

• Juvenile idiopathic arthritis

*Arthritis*

• Gout

**Infectious conditions with persistent** 

*Conditions predisposing to chronic infections*

*Immunodeficiency's predisposing to chronic infections*

• Common variable immunodeficiency

• Hypogammaglobulinemia • X-linked agammaglobulinemia

• Other immunodeficiencies

• Cyclic neutropenia

*Chronic infections* • Bronchiectasis • Osteomyelitis • Tuberculosis • Leprosy

• Chronic pyelonephritis • Whipple's disease • Chronic cutaneous ulcers

**Neoplastic diseases** *Blood malignancies* • Castleman's disease • Hodgkin's lymphoma

• Hairy cell leukemia *Solid tumors* • Hepatic adenoma • Renal cell carcinoma • Adenocarcinoma of the lung • Adenocarcinoma of the gut

• Mesothelioma

• Waldenstrom macroglobulinemia

*Diseases, associated with AA amyloidosis.*

• HIV/AIDS

#### **Infectious conditions with persistent inflammation**

*Conditions predisposing to chronic infections*


*Amyloid Diseases*

Immunoglobulin light chain

Immunoglobulin heavy chain

Leucocyte chemotactic factor-2

*nervous system.*

*Amyloidoses with renal involvement.*

**Table 1.**

**Protein precursor Fibril** 

**protein**

Serum amyloid A AA Chronic

Transthyretin ATTR Hereditary and

AL "Primary"

ALECT2 Not defined

Kidneys are the main site of involvement in AA amyloidosis, renal damage (**Figure 1**) occurs in 90% of cases, presenting with proteinuria, nephrotic syn-

**Clinical setting Kidney** 

AH LPD — All organs

amyloidosis, LPD

inflammation

as acquired or hereditary

Apolipoprotein A I AapoAI Hereditary Common Heart, liver, PNS, testis,

*LPD, lymphoproliferative disorders; CNS, central nervous system; PNS, peripheral nervous system; ANS, autonomous* 

acquired

Apolipoprotein A II AapoAII Hereditary Primarily Many organs

Apolipoprotein A IV AapoAIV Acquired Primarily — Fibrinogen α AFib Hereditary Primarily — Lysozyme ALys Hereditary Primarily Liver

**damage**

70% All organs

Primarily Liver

90% All organs except CNS

Common Heart, Eye, PNS, ANS,

larynx, skin

ligaments, tendon synovium, leptomeninges

**Other target organs**

Rheumatoid arthritis, if poorly controlled, still remains one of the most com-

However, many other conditions, listed in **Table 2**, may be causative for AA amyloidosis. Frequency of the diseases, associated with AA amyloidosis in the

Worthy to note, that beyond traditional causes, several rare conditions, such as sarcoidosis, cystic fibrosis and Castleman's disease, complicated by AA amyloidosis,

Moreover, we recently described a patient with sclerosing angiomatoid nodular transformation of the spleen and AA amyloidosis [8], association previously

Presence of NS or proteinuria in patients with the history of any kind of chronic inflammatory conditions, indicates a high "suspicion index' with AA amyloidosis. The diagnosis demands pathology confirmation with kidney biopsy, demonstrating not only positive Congo red staining of the material, infiltrating kidney tissue (see **Figure 1**), but also apple-green birefringence in polarized light (**Figure 7**) and

Treatment goal in patients with AA amyloidosis is a complete control of the inflammatory process [6]. Due to the various characters of the underlying diseases, treatment may include surgery, antibiotics, anti-TNF agents, colchicine and several novel drugs. Kidney transplantation for the patients with the end stage of renal disease (ESRD) is an important option and may be considered if a stable control of

mon inflammatory diseases, associated with AA amyloidosis (**Figure 2**).

drome (NS) and impaired kidney function [3, 6].

patients, followed in our unit, is shown in **Table 3**.

might be seen in the real practice (**Figures 3** and **4**).

unreported (**Figures 5** and **6**).

serum amyloid A expression (**Figure 8**).

the underlying disease has been achieved.

**78**


#### *Immunodeficiency's predisposing to chronic infections*


#### *Chronic infections*


#### **Neoplastic diseases**

*Blood malignancies*


*Solid tumors*


#### **Chronic non-infectious diseases with persistent inflammation**

#### *Arthritis*


#### *Bowel diseases*


*Systemic vasculitis*


#### **Hereditary autoinflammatory syndromes**

*Classic*

• Familial Mediterranean fever

*Rare*


#### **Table 2.**

*Diseases, associated with AA amyloidosis.*
