ARTICLE
Prurigo nodularis (PN) and macular amyloidosis (MA) are usually regarded
as distinct entities with different clinical and histopathological features.
Pruritus related scratching is believed to be the main cause of
PN, whereas its role in the pathogenesis of MA is questioned. We herein
report two cases with the combined occurrence of two conditions. Both
patients had intractable pruritus due to underlying systemic diseases.
The association of two otherwise uncommon dermatoses in pruritic patients
might be good evidence for the role of recurrent frictional trauma in
the pathogenesis of MA as well.
Case reports
Case 1
A 49-year-old Caucasian woman presented with numerous intensely pruritic
nodules on her arms and legs and hyperpigmented macules of 10 years duration.
She had a history of generalized pruritus that was the preceding factor.
Various antihistamines and topical steroids failed to show any improvement.
No similar skin eruption was reported in her family members.
Dermatological examination revealed more than 100 grey-brownish verrucous
nodules of 1-2 cm diameter on the entire skin; mainly distributed on the
extremities (Fig. 1).
Additionally, widespread hyperpigmented macules of rippled pattern were
located on the shoulders, trunk and upper back, distinctly sparing the
areas which had not been scratched (Fig.
2). On the trunk and the upper back, some of the verrucous nodules
were located on the hyperpigmented area. She had no history of using a
nylon brush or towels; she was scratching herself in the accessible areas.
Physical examination revealed marked pallor of the face, lips and the
palms.
One of the nodules on the right arm was excised totally. Histopathological
examination revealed orthokeratotic hyperkeratosis and acanthosis; suggesting
the diagnosis of prurigo nodularis. Crystal violet and Congo red staining
were negative. Histopathology of the punch biopsy material obtained from
the macular pigmented lesions on the shoulder showed orthokeratosis, increased
pigmentation in the epidermal basal layer, dense melanophages in the upper
dermis and sparse mononuclear perivascular inflammatory infiltration.
Deposits of amyloid were observed with Congo red and Crystal violet staining
in the papillary dermis.
Pruritus screening included a routine biochemistry panel (fasting blood
glucose level, BUN, creatinin, bilirubin levels, hepatic and thyroid function
tests), complete blood count and total IgE. Chest X-rays, stool examinations
for parasites and urinalysis were also done. The following laboratory
abnormalities were observed: Serum iron level: 35 mug/ml, serum iron binding
capacity: 435 mug/ml, ferritin: 14 ng/ml, erythrocyte sedimentation rate:
34 mm/h, hemoglobin: 6.2 g/dl, hematocrit: 20%, reticulocyte: 1%. Peripheral
smear revealed microcytic hypochromatous erythrocytes and poikilocytosis;
suggesting the diagnosis of iron deficiency anemia. Bone marrow aspiration
material was normocellular with erythroid/myeloid cell ratio of 1/3. Menometrorrhagia
was a prominent finding which would have led to the persistent loss of
iron.
The patient was treated orally with Tardyferon® dragees 2 x 1 (ferrous
sulfate 270 mg + mucoprotease 80 mg). Within one week, reticulocytes increased
to 4.8%. Hemoglobin level reached 8.5 g/dl at the end of the first month
and 12.6 g/dl 10 weeks after the beginning of the therapy. No improvement
in the pruritus nor in the cutaneous lesions occurred within this period.
Case 2
The second case was described previously [1]. A 60-year-old Caucasian
man with chronic active hepatitis presented with generalized pruritus,
itchy nodules and widespread pigmented macules of two years duration.
Symptomatic therapy failed to improve his chronic pruritus which was the
preceding factor.
On dermatological examination, a total of 8 dark-brown coloured verrucous
nodules of approximately 0.5-1.5 cm diameter on the trunk and extremities
were observed. Histopathologically, orthokeratotic hyperkeratosis and
acanthosis were the prominent features of the punch biopsy material obtained
from the nodule on the right pretibial area; suggesting the diagnosis
of prurigo nodularis. Crystal violet and congo red staining were negative.
Additionally, widespread itchy macular hyperpigmented lesions were observed
on the trunk and lower extremities with a symmetrical involvement of pretibial
areas. A grenz zone of several centimeters between the nodules and hyperpigmented
lesions was prominent (Fig. 3).
Histopathological examination of the punch biopsy material obtained from
the macules revealed orthokeratosis, increased pigmentation in the epidermal
basal layer, dense melanophages in the upper dermis and sparse mononuclear
perivascular inflammatory infiltration. Deposits of amyloid were observed
with congo red and crystal violet staining in the papillary dermis.
The patient did not survive his primary hepatic diesease and died after
6 months.
Discussion
It is well-known that PN develops as a consequence of pruritus-induced
chronic scratching. In a study, approximately 50% of PN patients were
reported to have an underlying systemic disease including liver abnormalities
that could be regarded as trigger factors of pruritus [2]. Cases with
underlying malignancies [3, 4] and uremia [5] were also reported. PN in
three patients with uremia was related to localized scratching and rubbing
of the skin [5]. In some cases PN is regarded as a traumatic chronic papulosis
of the skin [6]. Atopic diathesis has also been implicated as a contributory
factor in PN [7]. The major histopathological changes in PN are irregular
acanthosis and hyperkeratosis that are consistent with epidermal changes
due to recurrent trauma.
The role of recurrent scratching in the pathogenesis of MA is still
questioned. Familial cases [8], racial tendency [9], and association with
multiple endocrine neoplasia 2A [10] suggest a genetic background. Actually,
there is enough evidence to consider chronic scratching as the main cause,
perhaps on an unidentified genetic basis [11]: Amyloid in MA is supposed
to derive from degenerated tonofilaments of the necrotic keratinocytes,
as a result of epidermal damage [12]. Friction amyloidosis due to long-lasting
use of nylon brushes and rough towels [13, 14], the evolution from notalgia
paraestetica to lichen simplex chronicus (LSC) and to MA on the scapular/midscapular
area [11, 15, 16], and MA in patients with atopic dermatitis [17] are
examples supporting the role of chronic scratching in the pathogenesis
of MA. Furthermore, MA begins as macular lesions, and not infrequently,
persistent chronic scratching leads to additional epidermal changes such
as hyperkeratosis and acanthosis with formation of papules. As a result,
MA may change to LA via biphasic amyloidosis (BA) which is a linkage
period with clinical features of both MA and LA [18] The recent article
by Weyers et al. gives abundant evidence that LA is a result of
scratching and therefore represents a morphological variant of LSC and
PN [19]. The epidermal histopathological features of LA are similar to
those of LSC and PN; it only differs from them by the associated deposition
of amyloid. Considering the evolutionary stages from MA to LA, we believe
that MA is simply a response to scratching. The major difference between
MA and LA is the absence of epithelial hyperplasia in MA. In other words,
primary cutaneous amyloidosis (MA, LA, and the biphasic form), PN and
LSC are all manifestations of a chronic scratching process rather than
different entities.
In the present cases, the synchronous appearance of PN and MA mainly
points to the underlying pruritic disease as the common cause of scratching.
Chronic liver disease and iron deficiency anemia were the underlying abnormalities
in the presented cases which are frequently associated with generalized
pruritus [20].
The clinical appearance of the lesions showed some interesting features.
In both cases, lesions of PN and MA were mainly distributed on the frictional
areas. The reserved zone between the PN and MA lesions in Case 2 could
not be explained, but the sparing of the nonscratched areas in Case 1
could be attributed to the prevention of scratching of this skin area.
CONCLUSION
In conclusion, the synchronous appearance of PN and MA, distinctly sparing
the non-scratched regions, supports the essential role of pruritus related
scratching in their pathogenesis.
Article accepted on 10/1/00
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