Key words:
Congenital insensitivity to pain with anhidrosis, CIPA, Cough,
Musculoskeletal, Pain
To the editor:
Despite being an undesirable feeling, pain is one of the important
protective and defense mechanisms of the human body. Disorders that
affect pain sensation are associated with either increased or decreased
pain perception. Decreased pain perception could be acquired such as
diabetic peripheral neuropathy, syringomyelia, and infection (e.g.
leprosy); or congenital such as Hereditary Sensory Autonomic
Neuropathies (HSAN). (1). Congenital insensitivity to pain with
anhidrosis (CIPA) is characterized by insensitivity to pain and
temperature, decrease or absent sweating, hyperpyrexia, intellectual
disability, and self-mutilation which leads to variable injuries, due to
the involvement of the autonomic and sensory nervous system (2). Despite
most of the case reports were concerned with the orthopedic or other
conditions related to pain such as Anesthesia; there was no adequate
reporting of the respiratory disorders in such patients. Here, we
describe a 13-year-old girl presented with swelling of her right ankle
joint and foot (Figure 1). The swelling increased over the last few
days. The parents also complained that she was sleepy in the last few
days. She was previously diagnosed to have CIPA due to mutation of the
neurotrophic tyrosine kinase receptor type I (NTRK1) gene [homozygous
variant c.1842_1843insT (p. Pro6155ersf*12)].
Her past history revealed that she had frequent trauma either
accidentally or self-mutilated, with a history of a fracture in the
right foot 2 years ago to which she had posterior slab support. She had
also a history of recurrent episodes of high fever without sweating
especially with hot weather which usually calmed down after a bath or
cooling with a wet towel since birth. The family history showed that the
girl was the product of consanguineous marriage, with her sister and
maternal uncle have the same condition. Both parents are heterozygous
carriers of the same mutation (Figure 2).
She presented for consultation because of painless swelling of her right
ankle. Previous plain X-ray of the right foot and ankle did not show a
fracture. Her weight, height, and body mass index were 33 kg, 147.5 cm,
and 15.1 Kg/m2 respectively. General physical
examination revealed that she was conscious but not active like every
day, her Oxygen saturation was 90% on room air. Her gag reflex was
absent. Chest examination showed diffuse sibilant rhonchi all over the
chest with prolonged expiration. The parents denied the presence of a
cough at all and the child did not complain from any difficulty of
breathing. The chest X-ray was normal. Spirometry was done and showed
reduced forced expiratory volume in one second
[FEV1] (54% of predicted), forced vital capacity
[FVC] (77% of predicted), and reduced FEV1/FVC (57% of predicted).
After salbutamol inhalation, spirometry was repeated which showed
improvement of FEV1 (72%), FVC (83%), and FEV1/FVC
(69%).
After stabilizing her condition, we did an ultrasound of the right ankle
with Duplex. It showed diffuse asymmetrical swelling of the right ankle
with mild joint effusion and marked subcutaneous soft tissue edema with
trabeculation. Magnetic resonance imaging (MRI) complemented
with computerized tomography (CT) scan of her right ankle joint showed
skeletal immaturity with diffuse osteopenia. Within the distal tibia,
there were sequelae of old trauma to the distal tibia. There were
deformity and remodelling of the subtalar joints and the joints of the
midfoot. These findings were a combination of neuropathic changes and
altered foot and ankle mechanics. There were stress fractures within the
navicular, cuneiforms, cuboid, and several metatarsals, which explains
the foot swelling. There was no MRI evidence of osteomyelitis or septic
arthritis.
The child was prescribed Fluticasone dipropionate /salmeterol (125/25)
Evohaler; 2 puffs twice daily. She was also on physiotherapy, oral
anti-inflammatory Naproxin 250 mg twice daily for 5 days and advised for
limited weight-bearing until the swelling subsides. She came after 1
week, the swelling subsided completely, and her O2saturation was 95% on room air. After 1month, her pulmonary functions
were normalized.
The cough reflex protects the airways and lungs from aspiration, inhaled
irritants, particulates, and pathogens. It also clears the air spaces of
accumulated secretions. Cough is initiated by the activation of vagal
afferent nerves. Pain, dyspnoea, and cough share some important
features. Each of these symptoms is very common, can be profoundly
uncomfortable, and can strongly worsen the quality of life. Despite
being undesirable symptoms, both pain and cough are part of the
protective mechanism for the human body (3). At the level of the primary
afferent nerves, pain and cough pathways are remarkably analogous. As
with pain, cough can be evoked in experimental animals by stimulation of
nociceptive C-fibers as well as by faster-conducting Aδ-fibers. Cough
reflex can be impaired due to a wide variety of causes. In some diseases
of the central nervous system, there is a complete depression of
the cough reflex. Cough reflex sensitivity is also diminished in
smoking, pulmonary coccidioidomycosis and could be drug-induced as with
Baclofen-induced cough suppression (4).
As the cough reflex has type A and C fibers as an afferent limb; cough
reflex could be also affected in CIPA. According to the best of our
knowledge, unfortunately, we did not find any previous report describing
impaired pulmonary functions or diminished cough reflex in CIPA.
However, absent cough reflex was previously described in a female named
Ashlyn Blocker which gives the CIPA the name of Ashlyn congenital
condition. This girl was described that she had never sneezed and never
coughed (5). The importance of this report is to emphasize the need for
a high level of suspicion for the conditions presented with the cardinal
symptoms of pain, cough, or dyspnoea. Absence of these alarming
symptoms/signs in patients with CIPA should not let the physician
underestimate their clinical status; as serious conditions for instance
severe asthma, acute appendicitis, or even acute chest conditions could
present without its cardinal alarming signs. In all cases, we must ask
ourselves what should we treat: a symptom, a sign, or a disease?