ARTICLE
Dyskeratosis congenita (DC) is a rare genodermatosis that involves various
tissues. Males are affected more frequently [1]. It is a heterogeneous
disorder. Most cases are inherited as an X-linked recessive trait. This
disease has been regionally assigned to Xq28 [2]. The reticulated hyperpigmentation,
nail dystrophy and mucosal leucoplakia triad are major dermatological
signs. Many internal organ pathologies accompany the dermatological signs
and bone marrow hypoplasia is frequent [3]. Approximately 200 cases of
dyskeratosis congenita have been reported in the literature and association
with various malignancies is a well known phenomenon [4].
Case report
The patient was a 42-year-old man. His initial complaint was thinning
or complete disappearance of nail plates which started when he was 20
years old. The number of nails affected increased with age. When he was
28, cervical lymphadenopathy was noted and Hodgkin's disease (HD) was
diagnosed following cervical lymph node biopsy. A combined radiation-chemotherapy
(MOPP) regimen was started. No recurrence of Hodgkin's disease occurred
during his follow-up.
When the patient was 30 years old, reticulated hyperpigmentation of
the neck and upper body started and when aged 35, white lesions on the
oral mucosa became apparent. He complained of recent verrucous changes
in his oral lesions and presented at the dermatology department. The parents
were unrelated. There were no first degree relatives with dermatological
complaints, including his two children. No abnormalities were noted on
systemic evaluation.
On dermatological examination, widespread, reticulated hyperpigmentation
intermingled with a few centimeters wide, small, hypopigmented areas were
noted on the neck, upper part of the body and the back (Fig.
1). On the palms and soles, small hyperkeratotic areas were present.
The oral mucosa was covered with diffuse, white hyperkeratotic plaques
(Fig. 2). These were verrucous
in appearance and somewhat indurated on the hard palate. All of his nails
showed hypoplasia and dystrophy (Fig.
3).
Two skin biopsies were performed: one was taken
from the reticulated hyperpigmented area and the second from the interspersed
hypopigmentation. Histopathological examination of the two specimens revealed
essentially similar findings. These were basal keratinocyte vacuolar alterations,
eosinophilic bodies usually confined to the basal layer and upper dermal
melanophage accumulation. On the specimen from the hyperpigmented area,
the marked epidermal pigmentation, the many eosinophilic bodies and the
density of melanophage accumulation were striking. A biopsy from the oral
mucosa was also performed. Marked orthokeratotic hyperkeratosis and acanthosis,
as well as mild mononuclear inflammatory infiltration in the lamina propria,
were noted. No dysplasia was found.
On ophthalmological examination, epiphora was noticed. Laboratory examinations
revealed a mild increase in hepatic enzymes (sGOT: 57 U/L [5-42 U/L],
sGPT: 91 U/L [5-45 U/L]). Thrombocytes were 93.103/mm3.
Apart from these values, all biochemical and hematological tests were
within normal limits. HBsAg was positive. VDRL and anti-HIV antibodies
were negative. Conventional radiological examinations of the thorax, cranium
and pelvis, thoracic and abdominal CT scans did not show any pathological
findings. Osteoporosis was noticed on femoral bone X-ray. Gastroscopy
and rectoscopy examinations were normal.
Bone marrow biopsy showed normal hematopoesis. Liver biopsy was found
to be compatible with stage II chronic hepatitis B.
Discussion
The three major dermatological signs of DC become apparent during the
first two decades of life. Hyperpigmentation and nail dystrophy appear
in the first decade of life [4]. At least one of these features is present
by the age of 10 years in 92% of the patients [5]. Leucoplakia appears
in the second decade in most cases [4]. The first symptom in our case
was nail dystrophy, but with an appearance delayed to the end of the second
decade. Hyperpigmentation and leucoplakia occurred later than expected.
Other cutaneous and systemic manifestations
likewise exist. Bone marrow failure is considered to be a late manifestation
of DC [6]. Fifty percent of deaths in DC are due to infections related
to aplastic anemia [5]. Rarely, the hematologic signs may be the presenting
feature of the disease [6]. Hematologically, there are similarities to
Fanconi's anemia [3]. The earliest hematological abnormality in DC is
usually thrombocytopenia followed by anemia or pancytopenia [5, 7]. The
only pathological finding in the peripheral blood of our patient was thrombocytopenia,
but the bone marrow biopsy was normal. Thrombocytopenia may be the precursor
hematological sign but may also be related to chronic hepatocellular degeneration.
Although hepatic involvement presenting as hemosiderosis, fibrosis and
cirrhosis has been reported in 10% of DC cases, the etiopathogenesis of
these findings could not be evaluated [8]. The chronic hepatocellular
degeneration of our patient may be related to hepatitis B. The second
most frequent cause of death in DC are malignancies, with an association
rate of 30% [5]. Although the mean age of patients is 21 years at the
time of reporting, one or more tumors had already developed in 12% of
cases [5]. The third and fourth decades are the period when malignancies
reach peak incidence [4, 9, 10]. The cause of this increased tendency
towards malignant transformation in DC is not well understood, but chromosomal
instability and immunological abnormalities are thought to play a role
[11]. Squamous cell carcinoma is the most frequent malignancy reported
in DC [4]. This tumor can occur on leucoplakia or normal mucous membranes
and skin. Malignancies of the gastrointestinal tract and other visceral
organs or the hematopoietic system are also reported.
To the best of our knowledge, there has only been one case of DC associated
with HD reported in the literature [11]. This case had cutaneous and nail
changes, conjunctival leucoplakia and severe pancytopenia [11]. HD supervened
at 23 years and the patient died two years later [11]. There is another
report of an unaffected family member of a DC patient who died from HD
[12]. In our case, cutaneous findings of DC appeared later than expected
but HD was diagnosed in the third decade but did not relapse for 14 years.
An oral retinoid therapy for the oral lesions could not be started because
of chronic hepatitis. Interferon therapy was considered for the chronic
hepatitis. Long-term follow-up in order to detect other malignancies or
a recurrence of HD was planned.
The present case is the second one associated with HD and includes other
unusual features such as the delayed appearance of dermatological signs
and association with chronic hepatitis B.
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