Nail Bed: An Unusual Site of Diagnosis for a Heart Failure Cause

Question

We present a case of a 77-year-old male patient that was referred by a nephrologist. Patient's symptoms were cardiac insufficiency, ascites, pulmonary and lower extremity edema. The transthoracic echocardiogram and heart magnetic resonance showed left ventricle of 12 mm (6–10 mm) and cardiac septum of 13 mm (6–10 mm), ejection fraction of 31.7% (by Simpson's method), and myocardium infiltration pattern. This patient showed no kidney dysfunction (proteinuria = 0.08 g/24 h, creatinine = 0.8 mg/dL), nor signs of multiple myeloma − kappa protein value was 239 (170–370), lambda protein value was 174 (90–210), and relation kappa/lambda was normal: 1.06 (0.26–1.65) by both immunofixation and Freelite® method. Serum or urine immunofixation were normal. Rheumatoid factor was negative.

On dermatological examination, he showed no body ecchymosis, neither plaque, infiltrated lesions, or alopecia. However, he presented several nail dystrophies, with onycholysis, splinter hemorrhage, pachyonychia, red paronychia, onychomadesis, and one nail with an initial pterygium (see Fig. 1a), also visualized by dermoscopy (see Fig. 1b). A nail bed biopsy was performed on the first finger of the right hand after removal of the loose nail plate. On microscopic analysis, there were eosinophilic deposits in the lamina propria (see Fig. 2a). Special colorations were made (see Fig. 2b) showing apple-green birefringence under polarized light, confirming the diagnosis (see Fig. 2c).

Fig. 1.

a Clinical pictures showing nail involvement in this case. b Dermoscopy in the present case demonstrating onychomadesis and hemorrhage (first nail on the right hand, after removal of loose nail plate) and initial pterygium (fourth nail on the left hand).

Fig. 2.

a Eosinophilic deposits in the lamina propria; hematoxylin and eosin, ×400, highlighted by red arrows. b Positive Congo Red stain, ×400, pointed by red arrows. c Apple-green birefringence under polarized light, ×400, pointed by green arrows.

What is your diagnosis?

Answer

Systemic Amyloidosis

Amyloidosis is a systemic disease with multiple clinical manifestations because of the deposit of amyloid substance in many tissues and, in rare cases, nail involvement can be the unique cutaneous sign to confirm the disease and avoid overlooked diagnosis. Multiple nail changes were related to amyloidosis, such as longitudinal striations [1, 2, 3], onychorrexis [1, 2], splinter hemorrhage [3], pterygium simulating lichen planus [1, 4], pachyonychia [4], and destruction of the nail plate [5]. Our case did not show longitudinal striations as most cases did. It also showed onychomadesis, which was not described in the other cases in our review. A small number of cases were submitted to nail biopsy because other skin lesions may appear more frequently [2, 3, 4], or other sites can be biopsied, such as adipocytic tissue. However, particularly in hereditary amyloidosis, the sampling error can reach 60% of cases [6]. In this case, there were no other skin manifestations of the disease. Amyloidosis is a great cause of patient and family distress when a histological confirmation is not possible, even though there is a highly suggestive cardiac involvement such as in this case.

Some studies related more amyloid deposits on nail matrix than nail bed¹, but many cases showed deposits in both [1, 2]. In this case, the relatively less matrix involvement led to a nail bed biopsy. According to Haneke [2], nail as the only skin manifestation in systemic amyloidosis is related in just other 5 cases. These 5 cases occurred mainly in male patients (4:1) as the first presentation of systemic amyloidosis (all cases), and it can be related to multiple myeloma (3:2 with no underlying disease). Some studies indicated the improvement of the nail's lesions as a predictor of treatment response [1, 5].

Clinicians should be aware of nail involvement in systemic amyloidosis. It can precede systemic commitment, being a diagnostic spot and also a marker of treatment success. Nail biopsy is a safe, easy procedure, less invasive than myocardium, rectal, or salivary gland biopsies. More studies are necessary to understand this rare disease and propose new therapeutics, especially in hereditary forms. Based on this observation, careful nail analyses can be a good clue to amyloidosis diagnosis. As far as we are concerned, it is the sixth case of systemic amyloidosis with cutaneous manifestation restricted to the nail. The patient had been followed up for 6 months and unfortunately died from heart failure complications at the same time this manuscript was written.

Statement of Ethics

Ethics approval by the ethical committee is not necessary in case reports according to local guidelines once a written informed consent is obtained. Written informed consent was obtained from the patient's next of kin for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding sources to declare.

Author Contributions

Juliana Polizel Ocanha Xavier − dermatologist: conceptualization, diagnosis and follow-up, writing − original draft, review and editing, and visualization. Priscila Sayuri Kusano Yamamoto − nephrologist: follow-up, writing − visualization. Fábio Fumagalli Garcia − cardiologist: diagnosis (echocardiogram) and writing − visualization. José Cândido Caldeira Xavier-Junior − pathologist: diagnosis, writing − review and editing, and visualization.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author, Juliana Polizel Ocanha Xavier.

Funding Statement

No funding sources to declare.