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.
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
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