Nail alterations in patients aff ected by endemic pemphigus foliaceus in el Bagre, Colombia

© Our Dermatol Online 4.2019 325 How to cite this article: Abreu Velez AM, Upegui-Zapata YA, Valencia-Yepes CA, Upegui-Quiceño E, Jiménez-Echavarria AM, Niño-Pulido CD, Smoller BR, Howard MS. Nail alterations in patients affected by endemic pemphigus foliaceus in el Bagre, Colombia. Our Dermatol Online. 2019;10(4):325-328. Submission: 02.05.2019; Acceptance: 05.07.2019 DOI: 10.7241/ourd.20194.1 Nail alterations in patients aff ected by endemic pemphigus foliaceus in el Bagre, Colombia

A subclinical oral involvement [9], and in about one third of the patients, we discovered autoantibodies that appeared to be directed against the optic nerve envelope and its cell junctions [10], to cutaneous nerves and receptors [11], to the cell junctions of the cardiovascular system including its conductive system [12][13][14], and to cell junctions within the kidney [15]. In this study, we investigated nail abnormalities in patients affected by El Bagre-EPF as reported in the old Portuguese literature in patients affected by FS.

METHODS
The study was approved by a human quality assurance review board at the hospital in El Bagre, and all participants provided signed informed consent. We performed a case-controlled study of 40 patients with El Bagre-EPF and 40 healthy controls from the endemic area, matched by age, gender, race, demographics, comorbidities, and living and work activities. All subjects were evaluated clinically for the presence of nail alterations. The clinical examination was done independently by two board-certified dermatologists. Bacteriological and mycological studies were performed.
For ethical reasons, we did not take biopsies because the patients have to walk in the jungles, and work inside dirty rivers and creeks and biopsies with open shoes and a biopsy would increase their risk for overt infection especially, in the toenails of the lower limbs.

Direct Microscopy, Nail Stain and Mycology as Well Bacterial Studies
Before obtaining a specimen, the nails were clipped and cleansed with an alcohol swab to remove bacteria and debris. We studied for the presence of dermatophytes such as Trichophyton rubrum (T. rubrum), T. interdigitale (tinea unguium), for yeasts infections such as Candida albicans and for molds, especially Scopulariopsis brevicaulis and Fusarium species. We test for them using the standard 20% potassium hydroxide solution (KOH) technique. We clipped the nails from crumbling tissue at the end of the nail. The discolored surface of the nails was also scraped off. The nail debris was scooped out from under the nails for the culture.

Statistical Analysis
We used the Fisher exact test to compare two nominal variables (e.g. positive and negative presence of any nail alteration). We also compared the differences between patient cases and controls. p< 0.05 with 95% CI (or better) was considered statistically significant. For all statistical analyses, we used the software GraphPad QuickCalcs (GraphPad Software Inc., La Jolla, CA, USA).

RESULTS
The toenails were involved in 25/40 El Bagre-EPF and the changes in the nails were seen in patients with the chronic form of the disease (p < 0.05). Acute patients suffering El Bagre-EPF for less than six months showed no alterations. No patients hand finger nails were affected (p < 0.05). The more common nail alterations included change of color yellowish (Viera's sign) (25/40) (p < 0.05). This yellowish stain resembles the one seen as if dipped in iodine, Vieira's sign). None of the controls presented with the Viera's sign. Subungual hyperkeratosis was also very common 20/40) (Fig. 1), and was often associated with distal onycholysis (18/40) (p < 0.05). In 2/40 controls that had psoriasis, distal onycholysis was also observed (Fig. 1). Other toenails alterations included paronychia, onychorrhexis, onychatrophia in some areas of the area near the nail cuticle, and onychomadesis (most were often seen together) (18/40) in El Bagre-EPF patients, and no such changes were seen in controls. Onychogryphosis (nail thickening and scaling under the nail), common in the elderly, was seen equally in cases and controls (10/40) (Fig 1).

Direct Microscopy, Nail Stain and Mycology as Well Bacterial Studies
Direct microscopy, bacterial and fungal cultures were negative, except in one El Bagre-EPF patient who presented T rubrum in his foot toe nail and was treated accordingly.

DISCUSSION
Involvement of the nail unit in pemphigus is believed to be uncommon, especially in pemphigus foliaceus (PF) [16][17][18]. In this study, we found that in patients with a chronic El Bagre-EPF variant, the toenails are altered as described by the old Portuguese literature in patients affected by FS. We speculate that the cell junctions are targets within the nails in El Bagre-EPF patients, and are likely damaged by the autoantibodies; however, this is just speculation because for ethical reasons we did not perform biopsies. The can speculate that the toenails were affected because the continue trauma that these nails embrace due to the outside working activities of these patients often using open shoes. The autoantibodies, the continue inflammation and the trauma can make the toenails more prone for the clinical findings we observed. We were not able to determine the cause of the Viera's sign in this study.
With regards to the putative cause of the chronic paronychia we can speculate it to be a result of acantholysis of the lateral nail fold and the chronic inflammation in the adjacent dermis. With regards to the onychomadesis, we hypothesize that this may be the result of inhibition of normal nail plate growth and development; alternatively, the formation of blisters underneath the nail may result in detachment of the nail plate.
Unknown etiologies, predisposing factors and discrepancies evident in the current literature suggest that further investigation of endemic pemphigus foliaceus of the nail may result in additional clinical findings and may contribute to our understanding of the extent of the disease.

CONCLUSION
Our findings indicate that patients affected by El Bagre-EPF demonstrate significant toenail findings, especially in chronic cases. We suggest that the nails in the patients affected by other variants of EPF including FS and the Tunisian EPF need to be study.

Statement of Human and Animal Rights
None animal studies were perform.

Statement of Informed Consent
Informed consent was obtained from all patients for being included in the study. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.