Pregnancy occurring in AA amyloidosis: a series of 27 patients including 3 new French cases

First author :  Delplanque M et al 

Review: J Nephrol

Reference :  doi: 10.1007/s40620-024-02038-y 

PMID: 39266930

Link to article :  Pregnancy occurring in AA amyloidosis: a series of 27 patients including 3 new French cases - PubMed (nih.gov)

Introduction:

AA amyloidosis (AAA) is a multisystemic disease caused by the deposition of serum amyloid A (SAA) protein in tissues, which complicates chronic inflammatory conditions. It is a potentially life-threatening complication, with renal involvement being the most common manifestation. Pregnancy in women with chronic kidney disease is considered a risk factor for specific pregnancy complications and worsening of their underlying kidney disease. Data on pregnancy occurring during AA amyloidosis are limited, highlighting the importance of studying maternal and fetal outcomes. The objective of this study was to report pregnancy cases in patients with AA amyloidosis discussed within our reference center and to review the literature on the subject.

Patients and Methods:

Francophone cases were collected via the national multidisciplinary consultation on AA amyloidosis. A literature review was conducted using the MEDLINE and EMBASE databases. The analyzed data included maternal age, pregnancy complications, outcomes, and renal and inflammatory parameters.

Results:

Three new cases are described: a Turkish woman with familial Mediterranean fever (FMF) and postpartum nephrotic syndrome, a woman with cryopyrinopathy who had an uncomplicated pregnancy, and a Georgian patient with FMF, a kidney transplant recipient, whose pregnancy was complicated by infection and preterm delivery.

Results from the 3 New Cases and the Literature Review:

Among the 27 cases, including 24 from the literature and 3 new ones, 8 patients were diagnosed with AA amyloidosis during or just after pregnancy. The median age at diagnosis was 25 years [19-32]. FMF was the main cause of AA amyloidosis (19 cases), followed by cryopyrinopathies (2 cases), chronic inflammatory bowel disease (2 cases), and infections (2 cases). Renal complications were common: 33% (3/9) of patients with an eGFR < 60 mL/min/1.73 m² experienced renal deterioration during pregnancy; 66% (8/12) had increased proteinuria. Ninety-two percent (23/25) of patients had obstetric complications, including preterm birth (11/25), intrauterine growth restriction (10/25), preeclampsia (4/25), and hypertension (3/25). The median gestational age at delivery was 36.5 weeks [32.5; 38], mostly by cesarean section (17/22), and no hemorrhagic complications were reported. Two patients had undergone kidney transplantation before pregnancy. Estimated glomerular filtration rate (eGFR) was known before pregnancy in 10 patients, with a median of 55 mL/min/1.73 m² [38; 57], and 8/15 had significant proteinuria (> 0.5g/24h). Among those with known baseline eGFR before pregnancy, 33% (3/9) experienced a decline in renal function during pregnancy, but all recovered afterward. Two patients whose prior kidney function was unknown required hemodialysis. Proteinuria increased during pregnancy in 66% of patients (8/12).

Conclusion:

Pregnancy is a critical moment in the natural course of AA amyloidosis in terms of diagnosis and the risk of renal and obstetric complications. When possible, pregnancy should be planned with pre-conception counseling, multidisciplinary management, and close monitoring to minimize these risks.

Detecting Amyloid Goiter With 99mTc-PYPSPECT/CT in the Setting of Ankylosing Spondylitis An Uncommon Involvement of AA Amyloidosis

First author: Denizmen et al

Review: Clinical nuclear medicine

Reference : DOI : 10.1097/RLU.0000000000005280

Link to article : https://pubmed.ncbi.nlm.nih.gov/38967510/

Case Report:

The authors present the case of a 43-year-old Turkish man who had been followed for ankylosing spondylitis (AS) since the age of 16. He later developed severe AA amyloidosis with end-stage renal failure and underwent a kidney transplant. A 99m Tc-PYP scintigraphy was requested by his cardiologists due to an atypical appearance on a cardiac MRI. This scintigraphy showed minimal cardiac uptake of 99m Tc-PYP but a diffuse accumulation of the tracer in the thyroid gland (figure, panels A, B, and C). PET-CT images revealed increased uptake of 99m Tc-PYP in a diffusely enlarged thyroid gland containing regions with fatty density but no tracer accumulation (figure, panels D and E). There was no gastric contrast uptake, indicating the presence of free technetium (figure, panels F and G). Thyroid ultrasound showed diffuse gland hypertrophy with heterogeneous echogenicity, with hyper-echogenic areas closest to the transducer. A thyroid fine-needle aspiration biopsy revealed homogeneous eosinophilic deposits in the perifollicular region, Congo red-positive staining, and apple-green birefringence under polarized light, confirming amyloidosis (figure, panels J and K). Thyroid function was normal.

AA amyloidosis is a rare complication of spondyloarthropathies, with a reported prevalence between 1.1% and 2.15%. (1)

Amyloid goiter is a late complication of AA amyloidosis, mainly observed after renal amyloidosis, and can result in a rapidly growing goiter, potentially leading to clinical symptoms such as dyspnea, sometimes requiring decompressive surgery.

A study on amyloid goiters in AA amyloidosis secondary to familial Mediterranean fever showed that most patients (75%) were euthyroid, though alterations in thyroid hormone levels could be observed (2).

Conclusion: This is the first case demonstrating 99m Tc-PYP SPECT/CT uptake in an amyloid goiter in a patient with AA amyloidosis secondary to ankylosing spondylitis. This imaging technique could serve as a non-invasive tool to confirm the amyloid nature of a goiter in patients with confirmed AA amyloidosis.

References:

1. Papa R, Lachmann HJ. Secondary, AA, Amyloidosis. Rheumatic Disease Clinics of North America [Internet]. nov 2018 [cité 8 sept 2024];44(4):585‑603. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/S0889857X18300577

2. Vergneault H, Terré A, Buob D, Buffet C, Dumont A, Ardois S, et al. Amyloid Goiter in Familial Mediterranean Fever: Description of 42 Cases from a French Cohort and from Literature Review. JCM [Internet]. 5 mai 2021 [cité 8 sept 2024];10(9):1983. Disponible sur: https://www.mdpi.com/2077-0383/10/9/1983

A rare cause of AA amyloidosis: Hereditary epidermolysis bullosa

First author:  Chaabouni et al

Review: Néphrologie et thérapeutique

Reference :  DOI : 10.1016/j.nephro.2021.08.005

Link to article: https://doi.org/10.1016/j.nephro.2021.08.005

Introduction:

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disorder transmitted in an autosomal recessive manner. It is characterized by skin and mucosal fragility, leading to blister formation after minor trauma, with a cleavage occurring beneath the epidermis, under the lamina densa. It is associated with mutations in the COL7A1 gene, which encodes collagen VII, the main component of anchoring fibrils. RDEB manifests at birth with widespread skin blisters and erosions, accompanied by severe mucosal involvement.

The prognosis for RDEB is poor, and death usually occurs within the first three decades of life. Multiple complications arise, mainly malnutrition, recurrent infections, and the malignant transformation of chronic skin lesions into squamous cell carcinoma. AA amyloidosis, primarily affecting the kidneys, is a rare systemic complication of RDEB. In this article, the authors report two cases of renal AA amyloidosis in Tunisian patients with RDEB.

Case Reports:

Case 1:

The patient was a man born from a consanguineous marriage, diagnosed with RDEB. He presented with generalized blistering lesions since birth (Fig. 1). Severe mucosal involvement of the oral cavity was noted, though the scalp was unaffected. Electron microscopy of a skin biopsy revealed alterations in the anchoring fibrils. A mutation (p.R2063W/p.R2063W) in the COL7A1 gene was identified through Sanger sequencing. At the age of 38, the patient developed progressive lower limb edema that was white, soft, and pitting, which had appeared over two months, along with asthenia and oliguria. His blood pressure and cardiopulmonary examination were normal. Laboratory tests revealed hypochromic microcytic anemia (hemoglobin: 9 g/dL), end-stage renal disease, hypoproteinemia (46 g/L), and profound hypoalbuminemia (9.7 g/L). Urinalysis showed heavy proteinuria (4 g/24h) and hematuria (2+).

Given this nephrotic syndrome, renal AA amyloidosis was diagnosed based on the presence of amyloid deposits in the glomeruli and along the vascular walls, confirmed by renal biopsy. Hemodialysis was recommended but refused by the patient, who passed away two months later.

Case 2:

A 28-year-old woman, born from a consanguineous marriage, presented with pitting lower limb edema that had been present for one month. She had been followed for RDEB since birth. The skin examination revealed blistering lesions and post-blister erosions on the extremities and back. The healing process was slow, resulting in atrophic scarring without milia formation. There was no syndactyly.

Mucosal involvement included oligodontia (Fig. 2), and additional findings included toenail anonychia and cicatricial alopecia. Sequencing of the COL7A1 gene revealed a mutation (p.G1483D/pG1483D). Laboratory tests showed severe hypochromic microcytic anemia (hemoglobin: 7 g/dL), hypoproteinemia (42 g/L), hypoalbuminemia (18 g/L), and proteinuria (8 g/24h). Renal and hepatic function were normal.

A biopsy of the accessory salivary glands confirmed the presence of amyloid deposits.

Two months after diagnosis, the patient was admitted for a urinary tract infection caused by Escherichia coli. Her renal function rapidly deteriorated, with a creatinine clearance of 15 mL/min. The patient died a few days later from septic shock.

Discussion:

AA amyloidosis secondary to epidermolysis bullosa mainly complicates severe forms such as RDEB, due to chronic inflammation from recurrent skin infections.

Aside from hydronephrosis secondary to stenosing uropathies, other main causes of renal involvement in RDEB include post-infectious glomerulonephritis and mesangial glomerulonephritis with immunoglobulin A (IgA) deposition.

AA amyloidosis represents a severe, often fatal complication of RDEB.

Conclusion:

These two cases of AA amyloidosis in RDEB highlight the severity of this often fatal complication. Annual screening for proteinuria would allow for early diagnosis, and new treatments could improve the prognosis in these vulnerable patients.

Une cause rare et très sévère de l’amylose AA _ Les épidermolyses bulleuses héréditaires.p

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Fig. 1. Des lésions bulleuses et des érosions post-bulleuses du tronc chez notre premier patient (a), avec une syndactylie (b).

Authors	Year of publication	Number of cases	Amyloidosis-related disorders	Hemodialysis	Evolution
Chaabouni et al (1)	2021	2	Renal	Yes	Death of the 2 reported cases
Kaneko et al(2)	2000	7	Renal	Yes	Death of index case
Bourke et al(3)	1995	2	Renal	Unspecified	Death
Pinarbasi et al (4)	2019	1	Renal	Unspecified	Death
S yi (5)	1988	1	Renal	Unspecified	Death

References:

1. Chaabouni R, Amouri M, Chaari C, Bouattour Y, Sellami K, Bahloul Z, et al. Une cause rare de l’amylose AA : les épidermolyses bulleuses héréditaires. Néphrologie & Thérapeutique [Internet]. avr 2022 [cité 8 sept 2024];18(2):136‑9. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/S1769725521005319

2. Kaneko K, Kakuta M, Ohtomo Y, Shimizu T, Yamashiro Y, Ogawa H, et al. Renal Amyloidosis in Recessive Dystrophic Epidermolysis bullosa. Dermatology [Internet]. 2000 [cité 8 sept 2024];200(3):209‑12. Disponible sur: https://karger.com/DRM/article/doi/10.1159/000018384

3. Bourke JF, Browne G, Gaffney EF, Young M. Fatal systemic amyloidosis (AA type) in two sisters with dystrophic epidermolysis bullosa. Journal of the American Academy of Dermatology [Internet]. août 1995 [cité 8 sept 2024];33(2):370‑2. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/0190962295914366

4. Pinarbasi A, Dursun I, Daldaban B, Günay N, Çiçek S, Şahin N, et al. Epidermolysis bullosa complicated with nephrotic syndrome due to AA amyloidosis: A case report and brief review of literature. Saudi J Kidney Dis Transpl [Internet]. 2019 [cité 8 sept 2024];30(6):1450. Disponible sur: https://journals.lww.com/10.4103/1319-2442.275492

5. Yi S, Naito M, Takahashi K, Nogami R, Maekawa Y, Arao T. Complicating systemic amyloidosis in dystrophic epidermolysis bullosa, recessive type. Pathology [Internet]. 1988 [cité 8 sept 2024];20(2):184‑7. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/S003130251636634X