ARTICLE
Pemphigus vulgaris is an autoimmune bullous disease and is usually thought
to be an idiopathic condition. Reports of pemphigus induced or triggered
by drugs, nutritional factors and other exogenous substances have gradually
increased in the last few years [1-4].
Some authors suggest that even spontaneously occurring pemphigus is
often itself triggered by hidden exogenous factors [1]. They are capable
of causing intraepidermal acantholysis with or without involving immune
mechanisms. This opinion is supported by the fact that both idiopathic
and induced pemphigus show the same HLA pattern except for paraneoplastic
pemphigus. Recently, a new subgroup of induced pemphigus has been defined
as contact pemphigus and it has been suggested that contact dermatitis
leads to the onset of the disease [2].
In an epidemiological and survival study of 59 patients with pemphigus,
Krain reported 14 patients (29%),who had contact with various chemical
substances [3]. These patients, by virtue of their occupation, had been
exposed to miscellaneous, unidentified chemicals prior to the onset of
pemphigus. One of the patients of this group was described as suffering
from mercury bichloride poisoning with erosive gingivitis. He developed
pemphigus vulgaris one year after.
Case report
A 63-year-old Caucasian woman was referred to our clinic for the evaluation
of painful erosive lesions of her oral mucosa and blisters on the neck,
shoulders and sacral area. The lesions had appeared two months earlier
and impeded her eating. She was an agricultural worker and the blisters
developed when she was planting watermelons, using a pesticide dihydrodiphenyltrichlorethane
(DDT). She had used DDT-powder in a special kind of sack. The weather
was sunny and hot, but windy. The patient was dressed just in a bra and
shorts. She perspired profusely and particles of the pesticide stuck to
her skin. Twenty-four hours later bullae and erosions appeared on the
trunk and the oral mucosa.
At the time of admission, the woman had erosions all over her oral mucosa
which were covered with fibrinoid coating. She had specific foetor
ex ore. There were many bullae and other crusted erosions, located
on the trunk and sacral area.
All the laboratory tests were normal except ESR, which was 70 mm. The
histological examination of a biopsy specimen showed a subcorneal blister,
direct immunofluorescence revealed intracellular deposits of IgG(++) and
C3(+) in the epidermis. The titer of circulating antibodies was 1:80.
Patch testing performed with DDT, diluted with acetone 1:10 and 1:100
was negative after both 24 and 48 hours.
The patient was treated with methylprednisolone at an initial dose of
60 mg daily, and cyclophosphamide every other day at a dose of 2 g. We
used antiseptic and camomile solution for the local treatment of the oral
mucosa. The patient responded well to therapy. Low dose methylprednisolone,
8 mg per day was recommended on discharge. Since 1995, the patient has
been clinically healthy without any further treatment.
Discussion
Does topical contact with various substances induce or trigger pemphigus?
Contact pemphigus is a newly recognised subtype of induced pemphigus
in which a contact dermatitis seems to be the first step of the pathway
leading to the onset of pemphigus. The term "contact pemphigus" has been
proposed by Brenner et al. who stressed that pemphigus could be
provoked by topical contact with various substances [2].
The first case of contact pemphigus was probably described in 1970 by
Pirogova and Katyukhina [5] (Table
I). They reported a patient with clinical and histological data
for pemphigus vulgaris. Intriguingly, the development of new blisters
was just on Monday and Tuesday, accompanied by a heavy garlic odour. After
detailed observation, the doctors revealed that the patient used to apply
squashed garlic in order to obtain bullae and to provoke skin changes.
The diagnosis of self-mutilation was made and supported by the patch test
with garlic, which showed a bulla 2 cm in diameter, similar to the previous
ones.
In 1973 Lynfield et al. reported the
case of a 70-year-old man with a 3-year history of mild pemphigus erythematosus
[6]. After topical application of benzoin tincture as postoperative care
of a surgical intervention (basocellular carcinoma) he developed a number
of bullae around the wound. His past medical history revealed a thymoma
removal 13 years before. So we interpret this case as an aggravation of
previously diagnosed pemphigus by a topical substance.
In 1984, Dimitrova et al. reported a 62-year-old man, who developed
bullae just on the back after carrying big sacks filled with the pesticide
Baytan [7]. Because of the hot weather he worked naked to the waist.
In 1987 Tsankov et al. recorded a case of a 46-year-old man,
who developed pemphigus after a single oral contact with the organophosphate
pesticide Phosphamide [8]. The bullae were located solely on the oral
mucosa.
Tsankov et al. presented another case of contact pemphigus in
1990 [9]. A 25-year-old white man developed a vesiculobullous eruption
all over the body and oral mucosa after occupational contact with basochrom
(basic chromium sulfate).
Vozza et al. reported the case of a 23-year-old farmer who developed
pemphigus vulgaris two weeks after contact with the pesticide 1,3 dichloropropene
[10].
Bearing in mind all these cases, we carefully questioned all of our
pemphigus patients for some provoking factor. In our case, the contact
with DDT was followed by the development of numerous bullae. We believe
that the causative factor responsible for the outbreak of pemphigus is
indeed this substance. Our patient had used this chemical several years
ago.
DDT was the first synthetic pesticide which was created in 1942. Its
use has been forbidden in our country since 1973 because of its ability
to accumulate in the fatty tissues with subsequent toxicity.
In spite of this, sometimes private plant-growers use DDT illegally
when growing tomatoes, melons, watermelons, etc.
Chloroganic pesticides have a sensitising action
and play a role in the development of cutaneous allergic diseases.
In 1967 L.H. Criep [11] discussed the role of DDT and other irritants
in the development of allergic contact dermatitis and eczema of the hands
and forearms especially in homemakers, as a result of delayed contact
allergy.
In 1972, Mirakgmedov et al. using patch-testing experimented
on the role of DDT and its sensitizing action through the skin [12]. In
their study of 112 patients, they recorded 88 patients with acute dermatitis,
22 patients with subacute dermatitis and 2 patients with a toxic reaction.
Skin lesions were localised mostly on the photoexposed areas on the skin.
The authors discussed that this kind of dermatitis had an allergic pathogenesis
and was mainly seasonally predisposed.
In 1986, A. Fisher reported that chlorinated hydrocarbons including
DDT, in addition to their drying and irritating effect on the skin, may
produce chloracne [13]. DDT particularly may precipitate porphyria cutanea
tarda.
In our case, we suspect that the systemic absorption of the pesticide
after the topical contact was mainly responsible for triggering the immunological
mechanism. Through direct interaction with superficial cell molecules
and through different metabolic processes, the drug forms a neoantigen.
Due to this neoantigen or to the immunogen produced by the interaction
between hapten and selfcarrier protein, an MHC antigen is formed. As a
result of this, a specific identification of T-helpers occurs, certain
B cell colonies are activated and this leads to the production of pathogenic
antibodies.
With this case we add to the list of cases of contact pemphigus and
speculate that topical substances could be one of the likely factors for
induced pemphigus. From this point of view we would like to draw attention
to the importance of detailed history taking in pemphigus patients and
that contact pemphigus is a type of induced pemphigus.
REFERENCES
1. Brenner S, Wolf R, Ruocco V. Drug-induced pemphigus. I. A survey.
Clin Dermatol 1993; 11: 501-5.
2. Brenner S, Wolf R, Ruocco V. "Contact pemphigus". A subgroup of induced
pemphigus. Int J Dermatol 1994; 33: 843-5.
3. Krain LS. Pemphigus. Epidemiologic and survival characteristics of
59 patients, 1955-1973. Arch Dermatol 1974; 110: 862-5.
4. Tur E, Brenner S. Contributing exogenous factors in pemphigus. Int
J Dermatol 1997; 36: 888-93.
5. Pirogova EP, Katyukhina ZD. Artificial dermatitis caused by garlic.
Vestnik Derm Venerol (Moscow) 1970; 44: 53-4.
6. Lynfield YL, Pertschuk LP, Zimmerman A. Pemphigus erythematosus provoked
by allergic contact dermatitis. Occurrence many years after thymoma removal.
Arch Dermatol 1973; 108: 690-3.
7. Dimitrowa J, Obreshkowa E, Tsankov N, Zaimova Z. Pemphigus vulgaris,
induziert durch ultraviolette Strahlen und das Pesticid Baytan. Dt
Derm 1984; 32: 971-6.
8. Tsankov N, Dimitrova J, Obreshkova E, Lazarova A. Induzierter Pemphigus
(IP) durch das pestizid Phosphamid. Z Hautkr 1987; 62: 196-201.
9. Tsankov N, Stransky L, Kostowa M, Mitrova T, Obreshkova E. Induzierter
Pemphigus durch beruflichen Kontakt mit Basochrom. Dermatosen 1990;
38: 91-3.
10. Vozza A, Ruocco V, Brenner S, Wolf R. A case of "Contact Pemphigus".
Int J Dermatol 1996; 35: 199-201.
11. Criep LH. Nonmicrobial Delayed Response. In: Dermatologic allergy:
Immunology, diagnosis, management. Philadelphia, Saunders, 1967: 315-64.
12. Mirakgmedov UM, Karimov AM. The effect of pesticides on the skin
of agricultural workers. Vestnik Derm Venerol (Moscow) 1972; 96:
50-2.
13. Fisher A. Dermatologic hazards from "Newer" Synthetic Resins and
Certain Solvents. In: Contact dermatitis, Philadelphia, Lea &
Febiger, 1968; 127-40.
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