\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Heptaminol-Induced Hair Depigmentation in a Hemodialysis Patient}



\author[1]{Rym Zmiti}%
\author[2]{Noureddine Litaiem}%
\author[1]{Abderrahim Ezzedine}%
\author[1]{Faten Zeglaoui}%
\affil[1]{Charles Nicolle Hospital}%
\affil[2]{University of Tunis El Manar Faculty of Medicine of Tunis}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Heptaminol-Induced Hair Depigmentation in a Hemodialysis
Patient}

Zmiti.R\textsuperscript{1}, Litaiem.N\textsuperscript{1},
Abderrahim.E\textsuperscript{2}, Zeglaoui.F\textsuperscript{1}

1)~Dermatology department , Charles Nicole hospital, Tunis, Tunisia

2)~Nephrology department, Charles Nicole hospital , Tunis , Tunisia

\textbf{Abstract:} Hair depigmentation induced by heptaminol has been
rarely described. We report a case of a patient undergoing treatment
with heptaminol (heptamyl) who had chronic renal failure and had been
receiving hemodialysis since 2021. Reversal of the hypopigmentation
occurred upon cessation of the medication. The precise mechanism
underlying the alteration in hair color remains unknown.

Keywords: Heptaminol, hair, depigmentation, skin , chronic renal
failure(CRF)

\textbf{Introduction:}

Chronic renal failure (CRF) is associated with a variety of skin
manifestations. With the introduction of hemodialysis, life expectancy
extended and novel dermatological conditions are being observed as there
is more time for these changes to become evident. These skin alterations
incluse: xerosis, pallor, pruritus and cutaneous pigmentation . Other
cutaneous manifestations include Kyrle's disease ; pseudo-Kaposi's
sarcoma, calciphylaxis, uremic frost and purpura . The nail changes
include half and half nails. Hair changes include sparse body hair.
However, instances of hypopigmentation are rare. Patients with CRF are
typically prescribed multiple medications, some of which may provoke
cutaneous reactions. Hair color alterations can arise from various
genetic, metabolic, nutritional, and acquired disorders, with certain
medications capable of eliciting hair loss, stimulating hair growth, or,
infrequently, causing changes in hair texture and color{[}1--3{]}.

Herein, we present a case of acquired hair depigmentation in a patient
with chronic renal failure undergoing hemodialysis. The onset of hair
color change coincided with the initiation of heptamyl therapy and
reverted following discontinuation of the medication.

\textbf{Case history/Examination:}

A 40-year-old woman, classified as Fitzpatrick skin type III (Figure 1)
and CRF presented with hypopigmentation affecting the hair. She reported
no other medical history and no occupational exposure to chemicals and
lacked a family history of similar conditions.

In March 2021, the patient was diagnosed with a CRF of unidentified
origin, subsequently necessitating thrice-weekly hemodialysis sessions
since the aforementioned year.

In March 2023, she started treatment with heptaminol for hypotension
issues, with no concurrent use of other medications.

In June 2023, three months following the commencement of the medication
and two years subsequent to the initiation of hemodialysis, the patient
presented with the onset of hair depigmentation, affecting the eyebrows,
eyelashes, pubic hair and body hair (Figures 2 to7). Before commencing
the therapy, the patient had naturally black hair, a fact corroborated
by archived photographs. She denied any use of hair dye or bleaching
agents. No hypopigmentation was evident on his skin, and her nails and
mucous membranes appeared normal.

\textbf{Methods:}

There were no discernible clinical indicators of any other
abnormalities. Serological tests for HIV and Hepatitis C were negative .
In June 2023, heptaminol was discontinued after three months on
heptaminol. Remarkably, approximately one-month treatment
discontinuation, her hair resumed its original black coloration (Figure
8 to 13).we had the consent of the patient for the photographs and the
publication.

\textbf{Discussion:}

Advancements in hemodialysis have contributed to prolonged life
expectancy among CRF patients, affording opportunities for various
cutaneous manifestations to emerge.{[}2,4{]} A prospective study
involving 363 hemodialysis patients documented six cases wherein skin
and hair lightening occurred, observed between 10 months to 8 years
post-initiation of hemodialysis{[}5{]}. Similarly, Udayakuma et al.
identified hair abnormalities in 30\% of 100 hemodialysis patients,
characterized by sparse body hair and diffuse alopecia with dry,
lusterless hair, though no instances of hair hypopigmentation were
observed{[}2{]}.Hair color alterations can arise from changes not only
in melanin production but also in the hair structure itself, influencing
its optical properties. Typically, when the underlying cause is
rectified, hair color tends to normalize{[}6{]}.Drug-induced hair color
changes are infrequent adverse effects. While various drugs have been
linked to such alterations, robust evidence supporting a causal
relationship is often lacking. Chloroquine and certain cancer
chemotherapeutic agents exhibit stronger associations with hair color
changes. Other implicated drugs include p-aminobenzoic acid, calcium
pantothenate, anthralin, mephenesin, minoxidil, propofol, valproic acid,
and verapamil, yet further data are required for confirmation. Most
drug-induced hair color changes lead to lightening, although exceptions
such as PABA and select chemotherapy regimens may darken hair{[}7,8{]}.
The mechanisms by which drugs enter or modify hair remain uncertain.
While the precise mechanism underlying hair hypopigmentation remains
elusive, some cases have been linked to disturbances in phenylalanine
metabolism resulting in tyrosinase-inhibiting metabolites{[}4{]}.
Studies administering oral zinc sulfate, a tyrosinase inhibitor, to mice
have demonstrated significant hair shaft hypopigmentation{[}9{]}.

Four cases of lightening of hair in a dialysis patient under heptaminol
were reported {[}6,10{]} In our case, the temporal correlation between
hair lightening and subsequent normalization aligns closely with the
introduction and cessation of heptaminol, suggesting a plausible
association.

\textbf{Conclusion}

The case of our patient presents an uncommon occurrence characterized by
the onset of isolated hair hypopigmentation, manifesting two years after
the initiation of hemodialysis and three months following the heptaminol
initiation. Reversal of the hypopigmentation occurred after heptaminol
was discontinued.

Haut du formulaire\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image6/image6}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image7/image7}

\end{center}
\end{figure}

\textbf{Figures 3 to 7 :Hair fairness in Patient after 13 years of
hemodialysis and three months after starting heptamyl intake}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image8/image8}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image9/image9}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image10/image10}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image11/image11}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image12/image12}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image13/image13}

\end{center}
\end{figure}

\textbf{Figures 8 to13. Patient showing hair repigmentation after}

\textbf{discontinuation of the drug.}



\textbf{Author Contributions: All authors contributed to
conceptualization, writing, and editing of this review. They have read
and agreed to the published version of the manuscript.}

\textbf{Funding: No funding was utilized in writing this review.}

\textbf{Ethic statemenal t ''The patient gave her informed consent for
inclusion before she participated in the study. The study was conducted
in accordance with the Declaration of Helsinki.}

\textbf{Informed Consent Statement: we had the consent of the patient}

\textbf{Conflicts of Interest: The authors declare no conflict of
interest.}

\textbf{References:}

1. Pic\selectlanguage{ngerman}ó MR, Lugo-Somolinos A, Sánchez JL, Burgos-Calderón R. Cutaneous
alterations in patients with chronic renal failure. Int J Dermatol. déc
1992;31(12):860\selectlanguage{english}-3.

2. Udayakumar P, Balasubramanian S, Ramalingam KS, Lakshmi C, Srinivas
CR, Mathew AC. Cutaneous manifestations in patients with chronic renal
failure on hemodialysis. Indian J Dermatol Venereol Leprol.
2006;72(2):119\selectlanguage{english}-25.

3. Tajalli F, Mirahmadi SMS, Mozafarpoor S, Goodarzi A, Nasiri Partovi
M, Lakestani D. Mucocutaneous manifestations of patients with chronic
kidney disease under hemodialysis: A cross-sectional study of 49
patients. Dermatol Ther. juill 2021;34(4):e15015.

4. Hmida MB, Turki H, Hachicha J, Reygagne P, Rabier D, Zahaf A, et al.
Hypopigmentation in hemodialysis. Acquired hair and skin fairness in a
uremic patient undergoing maintenance hemodialysis: case report and
review of the literature. Dermatol Basel Switz. 1996;192(2):148\selectlanguage{english}-52.

5. Masmoudi A, Ben Hmida M, Mseddi M, Meziou TJ, Walha N, Hachicha J, et
al. {[}Cutaneous manifestations of chronic hemodialysis. Prospective
study of 363 cases{]}. Presse Medicale Paris Fr 1983. mars 2006;35(3 Pt
1):399\selectlanguage{english}-406.

6. Gharibi L, Zouhair K, Ramdani B, Benchikhi H. Hair lightening in an
hemodialysis patient treated by heptaminol (heptamyl). Dermatol Online J
{[}Internet{]}. 1 avr 2009 {[}cite 8 fevr 2024{]};15(4). Disponible sur:
https://escholarship.org/uc/item/1cb7d4mw

7. Bublin JG, Thompson DF. Drug-induced hair colour changes. J Clin
Pharm Ther. oct 1992;17(5):297\selectlanguage{english}-302.

8. Di Giacomo TB, Valente NYS, Nico MMS. Chloroquine -induced hair
depigmentation. Lupus. mars 2009;18(3):264\selectlanguage{english}-6.

9. Routhouska S, Gilliam AC, Mirmirani P. Hair depigmentation during
chemotherapy with a class III/V receptor tyrosine kinase inhibitor. Arch
Dermatol. nov 2006;142(11):1477\selectlanguage{english}-9.

10. Hendawy A. Hair Lightening of Three Hemodialysis Patients Under
Heptaminol. Exp Tech Urol Nephrol. 19 mars 2019;2.

\selectlanguage{english}
\FloatBarrier
\end{document}

