Dermatology: Practical and Conceptual


Opinion | Dermatol Pract Concept. 2025;15(2):5008 1

Is Tunisian Endemic Pemphigus Foliaceus A Real 
Entity, Or Should These Cases Be Reclassified  
With Other Autoimmune Blistering Disease?

Ana Maria Abréu-Vélez1, Willy Ramos2, Michael S. Howard1

1 Georgia Dermatopathology Associates, Atlanta, Georgia, USA

2 Instituto de Investigaciones en Ciencias Biomédicas (INICIB). Universidad Ricardo Palma, Lima, Perú

Key words: Tunisian endemic pemphigus foliaceus, Endemic pemphigus foliaceus (EPF), Pemphigus gestationis, Nosologic classification

Citation: Abréu-Vélez AM, Ramos W, Howard MS. Is Tunisian Endemic Pemphigus Foliaceus A Real Entity, Or Should These Cases 
Be Reclassified With Other Autoimmune Blistering Disease? Dermatol Pract Concept. 2025;15(2):5008. DOI: https://doi.org/10.5826/
dpc.1502a5008

Accepted: December 20, 2024; Published: April 2025

Copyright: ©2025 Abréu-Vélez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, 
distribution, and reproduction in any medium, provided the original authors and source are credited.

Funding: None.

Competing Interests: None.

Authorship: Both the authors have contributed significantly to this publication.

Corresponding Author: Ana Maria Abréu-Vélez, M.D., Ph.D., Georgia Dermatopathology Associates, 1610 Lavista Road NE; Suite 4, 
Atlanta, GA 30329, USA, ORCID ID:0000-0002-7692-4133, E-mail: abreuvelez@yahoo.com

Opinion

Endemic pemphigus foliaceus, also called South American 

Endemic Pemphigus Foliaceus (SAPF), has been described in 

Brazil, Peru, Venezuela, Paraguay, and French Guyana; the 

disorder presents primarily in native Indian and African de-

scendants living in rural areas [1]. In general, SAPFs pres-

ent similar sex predilection and familiar clustering [1]. In 

 Colombia, a new variant of EPF exists in El Bagre (El Bagre 

EPF) [1]. In a 1988 study in Tunisia (which did not state 

whether it was retrospective or not), Sfax hospital reported 

22 cases with pemphigus from the southern area of Tunis [2].  

They reported autoimmune blistering diseases (ABDs) in 19 

females (six presented with the disorder during pregnancy, 

and eight were post-partum breast feeding) as well as three 

males [2]. The authors stated that the age at presentation 

varied between 19 and 60 years, with an average age of  

30 years [2]. Seventy percent (70%) of the cases began by the 

age of 31, and 90% by the age of 45 [3]. The authors also 

cited a case of pemphigus vulgaris (PV) following radiation 

for skin carcinoma at the age of 60. Pruritus was reported 

preceding the rash in 14 cases [2]. The authors documented 

nine cases of mucosal involvement, and one case of likely 

mucous membrane pemphigoid [MMP] was recorded [2]. 

The histologic findings showed spongiosis in two cases, in-

cluding intraepithelial eosinophils and neutrophils [2]. The 

authors later suggested that seven cases could represent PV, 

six cases could represent pemphigus foliaceus (PF), six cases 

could represent seborrheic pemphigus (PS), two cases could 

represent pemphigus herpetiformis (HP), and one case could 

represent pemphigus vegetans [2]. Later, a 1993 study at the 

University Hospital of Sousse in Tunisia reported 20 cases of 

Tunisian Endemic pemphigus Foliaceus (TEPF), all of which 

involving young women seen from November 1985 through 

January 1987 [3]. The 1993 report claimed that pregnancy, 

postpartum, and/or breastfeeding conditions were present in 



2 Opinion | Dermatol Pract Concept. 2025;15(2):5008

several of the patients [3]. Later, in a 1995 report [4], similar 

authors emphasized the term TEPF, avoiding classification 

of their patient disorders as pemphigoid gestationis (PG) or 

other rashes presenting in pregnancy or postpartum states [4].  

In the 1993 [3] and 1995 [4] studies, differential diagno-

ses including drug-induced pemphigus and herpetiformis- 

type drug-induced pemphigus were not considered [3,4]. 

Moreover, few comments were offered about the presence 

of IgA intercellular staining (ICS) between epidermal kera-

tinocytes and/or immunofluorescence [IF] staining at the 

basement membrane zone (BMZ) described in several of the 

patients [3,4]. In summary, despite the presence of pregnancy 

and postpartum conditions reported in selected patients in 

the 1993 and 1995 studies, the authors did not review differ-

ential diagnoses involving pregnancy and postpartum condi-

tions and/or other causes of blistering diseases (BD) [5]. The 

first author of this letter (Amav) traveled to France in 1999 

to compare the reactivity of TEPF to those with El Bagre-

EPF in a laboratory that supposedly held TEPF samples; to 

her surprise, no sample was available for this comparison. 

Supposedly the 1995 study samples had been sent there. Fur-

ther, Amav contacted multiple times by email three authors 

on TEPF (Masmoudi [HM], Abida [OA], Masmoudi [AM]) 

raising these issues, but received no answer. Also, HM, OA, 

AM, and their other coauthors never discussed the presence 

of ICS using IgA, nor BMZ staining with IgG and C3 us-

ing IF [1, 3, 4]. No communication was received regarding 

differential diagnoses including IgA pemphigus triggered by 

medications, other ABDs and/or BDs caused by infectious, or 

other possible triggers. In 2013 [6], HM, OA, AM and others, 

including Drs. Stanley and Amagai (experts in ABDs), eval-

uated autoantibodies from healthy Tunisians and found that 

they reacted with the C-terminal extracellular domains of 

unmatured Dsg1 (pre-Dsg1) using immunoblotting (IB) [5].  

They concluded that anti-Dsg1 antibodies from healthy Tu-

nisians do not show ICS, in contrast to those from PF and 

or SAPF patients [6]. In lay terms, this finding contradicts 

the hypothesis that PF, PS, and SAPF antibodies are explic-

itly directed against the mature N-terminal extracellular 

expressed domain (mature form of Dsg1, and not the pre-

Dsg1, unmature form) [7]. Dr. Morini, who was part of the 

TEPF original study [3], made only one comment on this 

matter, calling the disorder “Tunisian pemphigus.” Neither 

Dr. Souissi nor Dr. Jomaa published further on TEPF. Later, 

in 1999, Dr. Pascal (an expert on ABDs) and colleagues ex-

amined Tunisian samples from 30 patients supposedly with 

TEPF using IB and immune electron microcopy (IEM), plus 

six with PV [8]. Overall, 7/30 TEPF sera were classified as 

PF (they bound to the 160 kDa/Dsg1 by IB; 2/6 PV sera 

bound to the 130 kDa Dsg3). IB and IEM showed that 24/30 

PF sera contained IgG1, IgG3, or IgG4 antibodies binding 

to a 185-kDa polypeptide localized on the desmosomal  

plaque [8]. The multiple publications by HM, OA, AM and 

their coworkers are clearly in contrast with others (which are 

referral centers for dermatological diseases) [8]. In 2011 [9],  

the presence of linear IgA bullous dermatosis (LAD) was 

described in Tunisian children [9]. Also in 2011, a larger 

study focusing on the incidence of ABD cases seen during an  

11-year period (1997–2007) reported 174 patients,  

(16.3 cases/year) with pemphigus, the most common ABD 

(53%); the majority were PV (61%) and 36% PF, followed by 

bullous pemphigoid (BP) in 41 patients (mostly younger males 

with occasional elderly patients) [9], PG in 18, LAD in 11,  

dermatitis herpetiformis in nine patients, and CP and epi-

dermolysis bullosa acquisita in two patients and one patient, 

respectively. They a1so reported single cases of pemphigus 

herpetiformis, paraneoplastic pemphigus, and IgG/IgA pem-

phigus [9]. Of 174 patients, 110 were female (63%) and  

64 male (37%), with a female-to-male ratio of 1:7 [9]. Pem-

phigus vegetans was observed in 10 patients, representing 

17.8% of the PV group. [9]. Epidemiologically noteworthy 

differences between SAPF and TEPF include the following.

a. Geographic: SAPF develops in low-income areas of the 

South American Amazonian humid areas near rivers and 

within the flight range of hematophagous insects [1-4, 

8, 10]. In contrast, TEPF occurs in rural areas with dry 

coasts in central Tunisia.

b. Affected age groups: SAPF mostly affects children, ad-

olescents, and young adults (except in El Bagre-EPF, 

mostly affecting males older than 25) [1]. TEPF seems to 

affect young women (reports varied) [1-3, 9].

c. The presence of familial cases: well-documented in SAPF 

[1, 10], although there is only one report in TEPF [11].

d. In TEPF, clusters of cases occur in olive fields, Turkish 

baths, in bovine workers, and with the use of traditional 

cosmetics [12]. SAPF occurs in association with bites 

from hematophagous insects, proximity to rivers and 

creeks, deforestation, and road construction [1, 10].

e. Additionally, female/male population demographics are 

clearly different in SAPF compared with the areas of 

 “endemicity” in TEPF, where females are more common 

than males [13].

For all the above reasons, we respectfully question the 

endemicity of TEPF. Furthermore, we invite the above three 

TEPF authors (HM, OA, AM) to further document field 

studies, including addressing infectious factors, and to an-

swer the above questions regarding TEPF.

Acknowledgements: We would like to thank Ms. Gildete 

Batista at the Serviço de Acceso á Informação Divissâo de 

Biblioteca e Documenção da Faculdade de Medicina da USP 

and Ms. Alessandra Carriel Viera, Analista Sociocultural/- 

Bibliotecaria, Instituto Lauro de Soussa Lima, Brazil.



Opinion | Dermatol Pract Concept. 2025;15(2):5008 3

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Sticky Note
AQ: References numbers are not in sequence. Please advise.