Pachyonychia congenita 
Clinical study 
PACHYONYCHIA CONGENITA 
A. Kansky, M. Penko and Z. Milakic-Snoj 
ABSTRACT 
Pachyonychia congenita (PC) is a rare dermatosis belonging to the broad group of hereditary palmoplantar 
keratoses. Judging by the reports in the literature it seems to be rare in large populations but is not that 
much rare in South-Slav peoples. The main symptoms are a substantially thickened nail-plate of greyish-brown 
color and a rough surface, follicular hyperkeratosis of the face and extensor surfaces of the proximal parts 
of extremities and also elsewhere, insular hyperkeratosis of palms and soles with blisters appearing at 
hyperkeratotic areas especially in summer, leukokeratosis of oral mucosa as well as other less important 
symptoms. Although a number of disorders may share certain common symptoms, the most serious diagnostic 
problems present candidiasis and epidermolysis hereditaria dystrophica dominans. 
The inheritance is assumed to be autosomal dominant, there are however certain observations which allow 
a somewhat different interpretation. These observations are reviewed in details. The true pathologic 
mechanism responsible for the disorder is not known. The methods for treating PC have been up to now 
rather, unsatisfactory. 
To make this problem apparent a Slovenian family with PC is presented. 
KEY WORDS 
pachyonychia congenita, symptoms, incidence, genetics, micromorphology, treatment, 
presentation of a family 
Synonyrns 
Pachyonychia congenita (PC), Jadassohn-Lewan-
dowsky syndrome, polykeratosis congenita (Touraine ), 
keratosis disseminata circumscripta, leukokeratosis 
linguae (1,2) 
General data 
Pachyonychia congenita (PC) is a rather rare form 
acta dennatovenerologica A.P.A. Vol 3, 94, No 3 
of hereditary palmoplantar keratoderma (HPPK). 
The first documented observation was made in 1904 
by Miiller (3) which was followed by Wilson (4) 
and Jadassohn and Lewandowsky (5) in 1906. Since 
then more than 250 cases were reported in the 
literature. Certain reports include a larger num?er 
of cases e.g. Moldenhauer and Ernst (6) reviewed 
93 cases and reported 6 newly detected, Puente 
mentioned 26 patients (7), Kumer and Loos 23 (8), 
153 
Pachyonychia congenita 
Su et al 12 (9), 14 cases were reported from 
Slovenia and 25 from Croatia (11). 
Clinical syrnptorns 
The main skin symptoms of PC are: an insular 
hyperkeratosis of palms and soles, a follicular 
hyperkeratosis primarily of the face and proximal 
parts of the extremities but also of other parts of 
the body, hyperhidrosis of palms and soles, periodical 
appearance of blisters especially during childhood, 
substantially thickened nail plates of brownish-grayish 
color and of a rough surface. Oral mucosa is 
usually also affected: on the tongue, buccal mucosa 
and sometimes also on the gingiva there are displayed 
smaller or larger areas of whitish hue (leukokeratosis) 
which should not be confounded with leukoplakia. 
If laryngeal mucosa is also involved a hoarseness 
results. 
Other more rare symptoms are prenatal dentition, 
eye symptoms as cataract or dyskeratosis of cornea, 
as well as cicatricial alopecia. 
The affected nails may already be observed during 
the first months of life (9,12) but they may appear 
later (9,10,13,14), Paller described 5 cases in which 
the disfigured nails became manifest during the 
second and third decade of life (15). 
Classification 
Due to so many different symptoms, which are by 
far not all expressed in every single patient, a 
number of classifications were proposed far PC. Far 
clinical purposes the classification proposed by Kumer 
2 3 4 5 6 
III 
2 
•- affected DO 
abortive case 80 
and Laos in 1935 (8) is suitable. According to it 
three groups of patients are recognized: Type A: 
thickened nails, hypekeratoses of palms and soles, 
follicular hyperkeratosis. Type B: same symptoms as 
in Group A plus leukokeratosis linguae and mucosae 
buccalis. Type C: same symptoms as in B and 
additional symptoms as dyskeratosis corneae, cataracta 
and others. 
Other classifications which deserve to be mentioned 
are those by Schonfeld (16), Sivasundram (17) and 
Feinstein et al (12). Certain authors believe that the 
designation pachyonychia congenita includes two 
distinct syndromes: Jadassohn-Lewandowsky in which 
leukokeratosis appears and that of Jackson-Lawler, 
characterized by natal teeth, epidermoid cysts, a 
possible corneal dystrophy but without oral leukoplakia 
(17 a). 
Based on their observations of 36 patients with 
PC, Kansky et al propose that symptoms in PC 
should be divided in major ones which are more 
frequent (palmar and plantar keratosis, thickened 
nails, follicular hyperkeratosis and hyperhydrosis) 
and minor symptoms as leukokeratosis, blisters as 
well as other rare manifestations (18). 
Incidence 
The PC being rare no data on the incidence in 
various populations are available. As this condition 
is relatively frequently encountered in the Slovenian 
population the incidence has been calculated. 
In Slovenia 14 cases were described in a population 
of 1.86 million which gives an incidence of 0.7 per 
105 inhabitants. For Croatia the analogous values 
3 4 • 5 
unaffected 
died in early infancy 
Fig. l. Genealogical tree of family O with Pachyonychia congenita 
154 acta dermatovenerologica A.P.A. Vol 3, 94, No 3 
Pachyonychia congenita 
Fig. 2. Patient O IIJ/5. Thickened nails at the age of 
1 ½ year. 
Fig. 4. Patient O JJJ/5. Leukokeratosis of the tongue at 
the age of 1 ½ year. 
acta dermatovenerologica A.P.A. Vol 3, 94, No 3 
Fig. 3. Patient O JJ/11. Thickened nails at the age of 
39 years. 
Fig. 5. Patient O II/11. Leukokeratosis of the buccal 
mucosa and tongue at the age of 39 years. 
Fig. 6. Patient O JJ/11. Follicular hyperkeratosis. 
155 
Pachyonychia congenita 
are 25 cases in 4.7 million which gives an incidence 
of 0.53 per 105 (10,11). 
Genetics 
The majority of authors consider that PC is caused 
by a mutation of a dominant autosomal gene (1,6,8,12), 
but, certain authors as Su (9) and Paller (15) are 
stressing a variable expressivity and an incomplete 
penetration. Although in many pedigrees a clear 
dominant inheritance is expressed there are pedigrees 
in which missing links are traceable and there are 
also isolated cases reported. For this reason different 
ways of inheritance are also mentioned in the 
literature. Cockayne (19) in 1933 and later Cosman 
(20) supposed that two genes were necessary for 
the expression of the disease, while Haber and 
Rose (14) accept even autosomally recessive 
inheritance. 
There are a few serious objections to the simple 
autosomal mode of inheritance in PC: 
l. almost ali pedigrees of PC patients are short 
2. missing links are relatively frequent in the pedigrees 
3. there is a number of isolated cases 
4. the ratio of affected to nonaffected family members 
which should be close to 1:1 was reported by 
Cockayne as 1:1.78 and in our observation it was 
even 1:4.48 
5. according to our observations in Slovenia and 
Croatia these patients originate from regions where 
people for centuries used to live in a secluded way 
and were marrying in the same or neighboring 
villages. 
6. it is also interesting to note that in large nations 
PC is extremely rare. 
The above listed observations are suggesting that 
the probability that two genes necessary for expression 
of PC being present in a patient, are rather low. In 
such a way our experience support Cockayne's 
assumption of two autosomally dominant genes 
determining the PC (19). However we have to wait 
until the problem will be solved by molecular biologists. 
Micromorphology 
Histopatology of the hyperkeratotic lesions of palms 
and soles in PC is closely related to the observations 
made in the HPPK Unna-Thost: hyperkeratosis, 
hypergranulosis, acanthosis, increased number and 
dilatation of capillaries in the papillary layer. Electron 
microscopic investigations revealed that the intercellular 
spaces of str. corneum are filled up with a clear 
acta dennatovenerologica A.P A. Vol 3, 94, No 3 
homogeneous mass as well as with remnants of 
keratinozomes and desmosomes 21. An increased 
number of tightly packed tonofillaments, enlarged 
and bizarre shaped keratohyline granules and many 
keratinosomes were observed in the cells of the 
granular layer. The sweat ducts were lined up with 
normal cells which were however surrounded by a 
few layers of keratinized cells. 
The relatively rare blister formation is initiated by 
a steadilly increasing perinuclear vacuolization in 
the cells of the upper Malpighian layer which results 
in the formation of an intraepidermal blister. 
The thickening of the nail plate starts in the 
matrix of the nail bed. Histological examination of 
the affected nails shows a marked increase in the 
thickness of the nail bed. Microradiographic inve-
stigations demonstrated an at least triple augmen-
tation of the dry substance per volume unit inside 
the nail bed: normally this dry substance amounts 
to 0.2-0.3 g/cm3, whereas in PC it exceeds 0.6 g/cm3 
(22). 
Keratinization 
Keratins are intermediate filament proteins which 
constitute the cytoskeleton of all epithelial cells. 
Over 30 such proteins are known and each is coded 
by a separate gene. They can be subdivided into 
two distinct classes on the basis of their migration 
in two-dimensional electrophoresis, their expression 
in different celi types and of their sequence homology. 
Type I keratins (KlO - K 19) are smaller ( 40-56,5 
kD) and relatively acidic, whereas type II keratins 
(K1 - K9) are larger (58-68 kD) and more basic. 
Usually keratins are expressed in pairs consisting of 
one type I and one type II polypeptide. The cluster 
of genes determining the type I keratins is located 
on chromosome 17 and that determining type II 
keratins on chromosome 12. 
Keratins K5 and K14 are present in the basal cell 
layer while in the differentiating epidermal cells Kl 
and KlO are expressed. In nonkeratizing squamous 
epithelia the cytoskeleton of the suprabasal maturing 
cells is formed from K3 and K14. During the last 
few years reports have been published suggesting 
that when keratin filament formation is perturbed in 
epidermal cells in transgenic animals, the keratinocytes 
become fragile and prone to rupture upon mild 
physical trauma (23). In hereditary epidermolysis 
bullosa (EBH) simplex a basal celi cytolysis occurs 
upon mechanical stress. It was discovered that patients 
with EBS have point mutations in the coding segments 
157 
Pachyonychia congenita 
of the genes encoding the basal epidermal keratins 
K5 and K14 (24,25,26). 
Epidermolytic hyperkeratosis ( erythrodermia ichthy-
osiformis bullosa, EH) is another autosomal dominant, 
blistering skin disease characterized · by mechanical 
stress-dependent suprabasal cell cytolysis. In this 
keratin disorder point mutations in the differentiation-
specific keratins Kl and KlO are involved (27,28). It 
was shown that mutations involving the rod domain 
are often deleterious to keratin filament network 
(29). 
Although great efforts are being made less exact-
information is available on molecular biology of 
HPPK. One of the reasons is the polymorphism of 
the respective keratin genes. Wild and Mischke (30) 
already in 1986 described keratins K4a, K4b, K5a 
and K5b, later data on keratins KlOa, KlOb, KlOc 
and KlOd were published (31). Tomic et al (32) 
who investigated the restriction fragment length 
polymorphism, were able by using the Msp I 
endonuclease to observe four alleles of keratin 5 
which they designated as a, b, c and d. Recently 
Rogaev et al (33) reported that they were able to 
map the causative genetic defect in HPPK to an 
8 cM interval on chromosome 17 ql2-24 or close to 
the keratin I type cluster. 
Lately it was published that K 16 is a candidate 
gene responsible for anomalies of keratinization in 
non epidermolytic palmo-plantar hereditary kera-
todermas (34). 
Differential diagnosis 
It is a long standing observation that thickened 
nails may be expressed in psoriasis, especially in the 
arthropathic form. Kansky and coworkers observed 
a thickened nail plate with subungual hyperkeratosis 
in 18 patients with HPPK Unna-Thost (34). But in 
the above mentioned conditions the nail plate does 
not display the thickness and the dark brown color 
as is observed in PC. Serious diagnostic problems 
may present certain forms of EBH dystrophica 
dominans with onychogryphosis as it was mentioned 
by Cockayne (19). 
Follicular hyperkeratosis in PC has to be diffe-
rentiated from keratosis pilaris, phrynoderma, from 
folliculitis in ichthyosis, pityriasis rubra pilaris or 
Darier's disease as well as from further similar 
conditions. Hyperkeratosis of palms and soles in PC 
should not be mistaken for HPPK Buschke-Fischer-
Brauer or for HPPK Unna-Thost. 
According to the authors' experience the most 
difficult problem is the differentiation of PC from 
158 
candidiasis of mucous membranes in children and 
from EBH dystrophica dominans in grown up persons. 
However taking into account ali the relevant symptoms 
of PC as well as the necessary laboratory tests both 
the above mentioned conditions can be excluded. 
Treatment 
There are various methods to treat hyperkeratoses 
with at least a temporary effect. Unfortunately up 
to now there is still no efficient procedure for 
treatment of the thickened nail-plate. A few attempts 
will be briefly discussed. 
LOCAL TREATMENT WITH KERATOLYTICS 
- ointment or cream containing 20% salycilic acid 
with an occlusive dressing 
- 3% solution of potassium sulphate and solution of 
potassium iodate in an equal amount of lanoline 
applied with occlusive dressing is another possibility 
for treatment of hyperkeratotic nails. 
- Wilkinson (35) suggests a nail avulsion ointment 
of the following composition 
urea 
salicylic acid 
distilled water 
aquaphor 
40.0 
20.0 
30.0 ml 
110.0 
(aquaphor contains 10% lanolin, 20% petrolatum, 
30% mineral oil and 40% water). 
Surgical avulsion of the nail under local or general 
anesthesia is a further possibility, but unless matrix 
has been removed the nail will regrow in the same 
shape. Cosman (20 ) proposed that the nail bed 
and matrix should be removed and the wound 
covered with a skin implant. Some patients preferred 
such solution to the abnormally thickened nail plate. 
X-ray treatment has also been applied, evidently 
without encouraging results (37). 
SYSTEMIC TREATMENT 
Etretinate or etretin were used in patients with 
PC by various authors. During the treatment the 
palmar and plantar hyperkeratoses have disappeared 
but recurred soon after the treatment was stopped. 
The nails were not influenced essentially 
Presentation of a family with pachyonychia 
congenita 
In order to make the presentation of PC more 
feasible a Slovenian family with PC is described. 
acta dermatovenerologica A.P A. Vol 3, 94, No 3 
;. 
Pachyonychia congenita 
Patient IUll and both of his children III/4 and III/S 
have typical clinical symptoms of PC. According to 
the history given by II/11, his mother (I/1) had a 
certain degree of palmoplantar keratoderma and 
most probably a thickened left toe nail. She gave 
life to 11 children, 5 of them died in childhood. 
Patient II/11 remembers his mother telling, him that 
his twin-brother who died in early infancy, also had 
thickened nails, however the other 9 siblings displayed 
no such symptoms. 
In ali three patients II/11, III/4 and III/S typical 
symptoms were expressed: pachyonychia, follicular 
hyperkeratosis, insular hyperkeratosis of palms and 
soles with blistering in summertime, hyperhydrosis 
as well as leukokeratosis of the buccal mucosa and 
of the tongue. The patient II/11 was 38-year old at 
the tirne of the first consultation, III/4 was four 
and a half and III/5 one and a half. They were 
invited far a check up 20 years later. 
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AUTHORS' ADDRESSES 
Aleksej 
160 
Kansky MD, PhD, professor of dermatology, Dpt Dermatology 
Clinical Center, Zaloška 2, 61000 Ljubljana, Slovenia 
Marta Penko MD, dermatologist, same address 
Zvezdana Milakic-Snoj MD, same address 
acta dermatovenerologica A.P.A. Vol 3, 94, No 3