Sildenafil is an effective therapy for treatment of chailblain in female patients with bacteriological study of ulcerative lesions

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Mustansiriya Medical Journal Volume 16 Issue 3 December 2017|
45
Sildenafil is an Effective Therapy for Treatment of Chilblain in Female
Patients with Bacteriological Study of Ulcerative Lesions
Prof. Dr. Khudhair Khalaf Al-Kayalli, M.B.Ch.B, F.I.B.M.S1; Burooj Mohammed Razooqi Al-aajem, M.Sc.2
1Department of Medicine, Dermatology, College of Medicine, Diyala University, Diyala, Iraq.
2Department of Microbiology, College of Medicine, Diyala University, Diyala , Iraq .
Abstract
Background: Chilblains, also called pernio or perniosis, are localized, tender,
inflammatory, erythematous, often itchy lesions, which may blistered or
ulcerated, caused by continued exposure to cold above the freezing point.
More commonly seen in children, women and persons with low body mass
index, with a genetic predisposition. Many prophylactic measures are used, and
therapeutic remedies for the treatment of developed chilblains, like nifedipine,
diltiazem, nicotinic acid derivatives, tamoxifen and minoxidil topically.
Objectives: The aim of the present study was to evaluate the effectiveness of
sildenafil in the treatment of chilblains in female patients.
Patients and methods: Sixty five female patients with chilblain were seen in a
private clinic in Kalar city, Al-Sulaimania Province, Iraq, for the period from the
first of October 2014 to the thirty of September 2016, their ages ranged from 10-
25 years (mean 16±8). The disease was diagnosed clinically and the patients
were evaluated for different data, and identification of bacteria which
complicate some patients with ulcerative lesions and all patients treated by
sildenafil tablet (50mg, once daily after meal), for 7-10 days and assisted
clinically (subjectively) for resolution of the disease.
Results: Sixty patients (92.3%) out of (65) studied patients shows complete
clearance of the disease clinically within 7-10 days of sildenafil treatment (50mg,
tablet, once daily orally after meal). Five patients (7.7%) shows partial
improvement of the disease with persistence of the signs and symptoms.
Staphylococcus aureus was isolated from 20(30.76%) patients. Ten patients
(15.4%) developed flushing and hotness of the face with nasal stiffness and 5
patients (7.7%) developing gastric upset.
Conclusion: It was concluded that sildenafil was an effective therapy for the
treatment of chilblain in female patients, although it was associated with some
side effects.
Date Submitted: 18/4/2017
Date Accepted: 10/9/2017
Address for Correspondence:
Prof. Dr. Khudhair Khalaf Al-Kayalli
M.B.Ch.B, F.I.B.M.S, Department of
Medicine, Dermatology, College of
Medicine, Diyala University, Diyala,
Iraq
E-mail: khudhair.derma@yahoo.com
Key words: Chilblain, nifedipine, diltiazem, sildenafil, flushing
INTRODUCTION
Chilblains, also called pernio or perniosis, are localized,
tender, inflammatory, erythematous, often itchy lesions,
which may be blistered or ulcerated, caused by
continued exposure to cold below the freezing point.[1,2]
Dampness and wind that increase thermal conductivity
and convection play a part, absolute temperature is less
important than the cooling of nonadapted tissue and the
condition shows a genetic predisposition.[1] Chilblains
have been described most often in temperate regions,
where winters are occasionally cold and damp, and are
seen less often in very cold climates, where well-heated
houses and warm clothing are available. Both
acrocynosis and chilblains appear to be more common
in children, women, and persons with low body mass
index, pregnancy may have a beneficial effect on
chilblain.[3] Immunohistochemistry revealed increase in
nerve bundles in the papillary dermis.[4] However,
Research Article

Al-Kayalli et al.: Sildenafil Treatment of Chilblain in Female Patients
Mustansiriya Medical Journal Volume 16 Issue 3 December 2017 |
46
chilblains do not always occur at the time of maximum
cold.[5]
Chilblains develop acutely as a single or multiple,
burning, erythematous, or purplish swellings. Patients
may complain of itching, burning, or pain, in severe
cases blisters, pustules and ulceration may occur.
Characteristic locations include the proximal fingers and
toes, planter surfaces of the toes, heels, noses and ears,
but other sites like calves and thighs can be affected.[1,6-
8] Lesions usually resolved in 1-3 weeks, but may
become chronic in elderly people with venous stasis.[9]
Tight garments such as gloves, stockings and shoes are
especially to be avoided in cases in which, there is also
peripheral vascular diseases.[1,10] Chilblains can be
idiopathic (spontaneous and unrelated to an other
diseases), but may also be a manifestation of another
serious medical condition that need investigations, e.g.
systemic lupus erythematosus.[1,9] Idiopathic perniosis is
characterized histologically by edema of the papillary
dermis and the presence of superficial and deep
perivascular lymphocytic infiltrates, necrotic
keratenocytes and lymphocytic vasculitis also have been
reported.[1,6,11,12]
The most important point in the management of
chilblains is prophylaxis, through the use of adequate,
loose, insulating clothing and appropriate warm housing
and workplace. Maintaining the blood circulation by
avoiding immobility is also helpful, a short course of
ultraviolet light therapy at the beginning of winter is
recommended, avoid rapid changes in temperature,
soaking in warm water with Epson salts for 15-20
minutes, 3-4 times a day and avoid very hot water.[1,6,13]
Once chilblains occur, treatment is symptomatic with
rest, warmth and topical antipruritics (topical steroid
creams), calcium channel-inhibiting drugs may be
effective in the treatment of sever recurrent perniosis
(e.g. nifedipine), diltiazem, nicotinic acid derivatives,
tamoxifen and minoxidil topically as a vasodilator may
also be used,[14-17] In cases of crippling severity,
thyrocalcitonin and heamodilution may be helpful.[1]
Sildenafil is one member of phoshpodiesterase type-5
(PDE5) inhibitors, which hydrolyses cyclic guanylate
monophosphate specifically to 5 guanylate
monophosphate, promoting corporal vascular relaxation
and penile erection in response to sexual stimulation.
Oral PDE5 inhibitors have afforded effective and well
tolerated treatment for erectile dysfunction. PDE5 have
a potential benefits in divers non-sexual applications,
including, cardiovascular, pulmonary, cutaneous,
gastrointestinal, neurological and reproductive
disorders.[18] Sildenafil is used in the treatment of
Raynaud's phenomenon resistant to vasodilator therapy
in dose of (50mg) twice daily for one month.[19] The aim
of the present study was to evaluate the effectiveness of
sildenafil in the treatment of chilblains in female
patients.
PATIENTS AND METHODS
Sixty five female patients with chilblain (perniosis)
were seen in a private clinic in Kalar City –Al-
Sulaimania Province, Iraq, for the period from first of
October 2014 to the thirty of September 2016. Their
ages ranged from (10-25) years with a mean age of
(16±8) years, all patients were females, because males
were excluded from the study due to sexual excitation in
males. The disease was diagnosed clinically, and all
patients were attended the clinic during the winter time,
where the temperature around zero C°. They were fully
interrogated regarding the age, job andoutdoor working,
exposure to cold weather and damping, humidity,
previous history of the same disease and therapy used,
family history of the same condition and personal and
family history of other medical disease, like systemic
lupus erythematosus, systemic sclerosis, Raynaud's
phenomenon and disease and hypercrioglobulinema, to
be excluded from the study, so all patients had idiopathic
chilblains. Clinically patients had either bullous, erosive
and ulcerative lesions, or only erythema and swelling
with sever itching. Some patients with ulcerative lesions
developed secondary bacterial infection, and swabs
were taken from them, and cultured on different culture
media and submitted to a serial of different biochemical
tests for diagnosis of type of bacteria which cause
infection. All patients were treated by sildenafil tablets
(50mg once daily orally after meal) for 7-10 days, and
those with bacterial infection were treated by cefexem
400mg daily, orally for 7 days, and all patients were
assisted clinically after the course of treatment, to
evaluate the response of the disease to the therapy, i.e.
the evaluation was subjective according to the clinical
assessment by the dermatologist and patients
satisfaction. If the lesions and symptoms were
disappeared, means the response was complete, and if
some signs and symptoms were persisted, the response
was partial.
RESULTS
The study revealed that the patients had an idiopathic
chilblain (i.e. non of them had medical disease
associated with chilblain), with clinical features
consisting of erythema, swelling of the fingers and toes
in 40 (61.54%) patients (figure-1), and some patients 25
(38.46%) had bullea, erosions and ulcerations,
associated with sever itching and burning sensation
(figure-3) and 20 (30.76%) patients of those with
ulcerative lesions developed secondary bacterial
infections. Sixty patients (92.3%) out of (65) patients,

Al-Kayalli et al.: Sildenafil Treatment of Chilblain in Female Patients
Mustansiriya Medical Journal Volume 16 Issue 3 December 2017 |
47
shows complete clearance of the disease, within 7-10
days of treatment with sildenafil (50mg tablet once daily
orally) (figure-2,4) and (5) patients (7.7%) shows partial
improvement with persistence of erythema, swelling,
itching, burning sensation and sometimes erosions and
ulcerations. Bacteriological study of those with
secondary bacterial infections, only staphylococcus
auraus was isolated. Ten patients (15.4%) developed
flushing and hotness of the face with nasal stiffness and
(5) patients (7.7%) developed gastric upset.
Figure 1: Chilblain of feet with erythema and swelling
before treatment.
Figure 2:Patient in figure-1 after treatment with sildenafil.
Figure 3: Chilblain of foot with erosive, bullous and
ulcerative lesions with infection, before treatment with
sildenafil and cefexem.
Figure 4: Patient in figure-3 after treatment with sildenafil
and cefexem.
Table shows Clinico - soscio-demographic information of the patients
Total
No
Patients with
swelling, edema,
erythema
Patients with
erosions and
ulceration
Complete
clearance
Partial
improvement
Side effects
Bacterial
infections
No
%
No
%
No
%
No
%
No
%
No
%
65
40
61.54
25
38.46
60
92.3
5
7.7
15
23.1
20
30.76
DISCUSSION
We Chilblains were a relatively common skin disease in
countries with cold winter, and more common in
females than males, specially in teen ager groups, most
probably due to hormonal changes at menarche ages of
female patients. Also the disease was most commonly
seen in outdoor workers, due to excessive exposure to

Al-Kayalli et al.: Sildenafil Treatment of Chilblain in Female Patients
Mustansiriya Medical Journal Volume 16 Issue 3 December 2017 |
48
cold weather and in those with genetic predisposition to
develop the disease. Regarding the age and gender the
study was concordant with other study.[1,10] Regarding
the study there was a limited number of studies in which
sildenafil used to treat patients with chilblains, although
sildenafil was used as trial in the treatment of Raynaud's
phenomenon and disease, which were resistant to
vasodilator therapy and giving a good results and
satisfaction by the patients using this drug.[26] Chilblains
were caused by exposure to cold around freezing point,
which cause vasoconstriction of peripheral blood
vessels and appearance of signs and symptoms of the
disease and the disease resolute spontaneously with in
(1-3)weeks with discontinuation of exposure to cold, so
the use of therapy was to control the disease in presence
of exposure to cold and the mode of action of sildenafil
was most probably through vasodilatation of the
peripheral circulation and improvement of perfusion,
which result in improvement of chilblains and resolution
of signs and symptoms.[25] Staphylococcus aureus was
the only bacteria isolated from the lesions with bacterial
infection, most probably due to the staphylococcus
aureus carrier state in a bout (35%) of general
population, the results was concordant with other
studies.(1) Because the effects of sildenafil were not
restricted to the skin and may result in some troublesome
side effects, but it appears in this study to be an effective
therapy in chilblains with cure rate of (92.3%). In
comparison with other drugs used in treatment of
chilblain,[21-24] like nifedipine, diltiazem, tamoxifen, and
nicotinic acid, in which response of the disease ranging
from 50-85%, sildenafil appears to be more effective,
specially for severe and resistant cases and those with
erosions and ulcerations. Conclusions: It was concluded
that sildenafil was a good therapy for treatment of severe
and resistant cases of chilblains, although may be
associated with some side effects.
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