Keywords
congenital insensitivity to pain with anhidrosis - total hip arthroplasty - femoral
neck fracture - dual mobility cup - hereditary sensory autonomic neuropathy
Introduction
From a biological point of view, pain is a necessary protection mechanism for our
tissues, and a lack of pain perception may cause severe problems. There are two groups
of conditions that are characterized by the congenital absence of pain perception:
hereditary sensory autonomic neuropathy (HSAN) and hereditary nonneuropathic analgesia
(HNNA).[1] HSAN is a clinically and genetically heterogeneous group of disorders of the peripheral
nervous system characterized by congenital malfunction of sensory and autonomic nerves.
In 1993, Dyck[2] classified HSANs into five types by taking into account their functional aspect
and other factors, such as mental retardation (when tested, intelligence quotients
[IQs] varied from 41 to 78, the majority being in the 60s; microcephaly was sometimes
reported), oral lesions, touch/temperature sensibility, tendon reflexes, production
of tears/perspiration, and histopathology of the nerves. On the other hand, patients
affected by HNNA have an adequate transmission of the painful stimuli, although they
are unable to elaborate them centrally. They are usually normal with respect to intelligence,
motor development, nerve histology, and perception of other senses compared with their
siblings.[3]
[4]
Congenital insensitivity to pain with anhidrosis (CIPA), also known as HSAN type 4,
is an extremely rare autosomal recessive disorder caused by a polymorphic mutation
of the gene, NTRK1 that encodes a receptor for the nerve growth factor (NGF). The
mutation leads to autonomic and sensory nerves malfunction with insensitivity to both
deep and superficial painful stimuli, inability to sweat and produce tears, and mild
to moderate mental retardation with self-mutilating behavior. It was initially described
as a syndrome where the entire body was affected by congenital absence of pain sensitivity,
although other sensory modalities were intact or minimally impaired and tendon reflexes
were present.[5] Children affected by CIPA fail to sweat (anhidrosis) and produce tears and suffer
from multiple fever episodes, corneal ulceration with poor healing potential, and
repeated traumatic and thermal injuries. Height and weight are below normal percentile
for their age. The oral manifestations include premature loss of teeth due to biting
hard toys, lips, and fingers.[3]
[6]
[7]
[8] Intraoral fibrous scars in cheeks decrease the mouth opening. Abnormalities of the
joints (Charcot joints) are often present and must be surgically corrected. Hyperthermia
is a major cause of death during the initial years. As these children grow, accidental
injuries, such as falls or burns lead to multiple scars, as well as articular dislocations
and bone joint fractures that can ultimately predispose to deep infections.[8] Most of the complications occur at the lower limbs, although all joints can be affected.
Fractures occur in the early years of life, especially between the age of 4 and 6
years, due to intense activity. The causes of most fractures and dislocations are
not well documented; some are caused by minor trauma, such as short falls. This suggests
that CIPA patients may sustain injuries from minor traumas that would not result in
injuries in normal children. Video gait analysis of young patients affected by CIPA
reported an altered walking, which may contribute to the high incidence of injuries
in the lower limbs.[9]
This report presents the surgical treatment for a severe osteonecrosis of the femoral
head, secondary to an inveterate neck fracture, in a young male affected by CIPA.
Case Presentation
The particular form of this case report and the fact that no experimentation was performed
made the approval of the local ethics committee unnecessary. Nonetheless, all the
authors declared to have managed this case in respect of the Italian laws and of the
Declaration of Helsinki.
Our patient, a 21-year-old Caucasian boy, was the first child of consanguineous parents
(second-degree cousins). He was delivered normally after an uneventful pregnancy,
weight at birth was 3.250 kg. From the first week of life, he had several unexplained
bouts of fever, and as reported by his mother, he was always “hot and dry.” At 10
months of age, when he began to crawl, the parents noticed bruises with some ulceration
on him. At that age, he was diagnosed with CIPA and from that moment on, very accurate
care was provided to him by his parents, relatives, and all his teachers with high
attention on trauma during the school and game. Luckily, he was able to grow until
the age of 18 years without having major injury, except for some dental problems and
an episode of traumatic corneal lesion at the age of 11 years.
He arrived at our attention for a functional limitation of the left hip, referring
that he was unable to walk for more than two or three steps. At admission in our orthopaedic
department, he appeared as an aware and cooperative guy with dry warm skin. His body
temperature was 36.7°C, height was 166 cm, weight was 63 kg, and head circumference
was within normal limits. The teeth were almost all present with slightly hypertrophic
gums. There were some very small ulcerations in the internal side of the cheeks. Evaluation
of intellectual development was a bit difficult because of his shyness. Tested IQ
was 76. Neurologic examination founded moderately depressed tendon reflexes and a
lack of reaction to painful stimuli, such as pinpricks or compression of the muscles
or tendons. However, he seemed to perceive tactile stimuli. Sensitivity to temperature
or vibration was not tested. Routine blood count, serum electrolyte, coagulation,
and hepatic and renal function values were normal. At clinical examination, the left
hip was slightly shortened (0.5 cm), abducted, and externally rotated with a limited
range of motion (ROM).
Chest X-Ray and ECG did not show alterations. X-rays of the pelvis and left hip showed
a severe necrosis of the femoral head with deformation and resorption in an inveterate
femoral neck fracture ([Fig. 1]). Harris Hip Score (HHS) was 61 points.
Fig. 1 Anteroposterior weight-bearing radiograph of the pelvis (A) and axial radiograph of the left hip (B) showing a severe necrosis of the left femoral head with deformation and resorption
in an inveterate femoral neck fracture.
Despite the young age of the patient, we decided to perform a total hip arthroplasty
(THA) through a posterolateral approach. A severe osteoporosis was found intraoperatively
with a total resorption of the femoral head ([Fig. 2]); therefore, we opted for a cemented stem (MS-30 size 6 with 22 mm/+0 metal head;
Zimmer Biomet Inc; Warsaw, Indiana, United States) and a cemented double mobility
cup (UHL diameter 44/22 mm; Groupe Lépine; Lyon, France), both fixed with antibiotic-loaded
cement (GMV gentamicin cement; Johnson & Johnson Depuy; Warsaw, Indiana, United States;
[Fig. 3]). Cemented implant provided an immediate weight bearing to the patient, unabled
otherwise to handle partial loads, and reduced the risk of aseptic loosening that
would not be referred by the patient.
Fig. 2 Intraoperative image showing a severe osteoporosis with a total resorption of the
femoral head.
Fig. 3 Anteroposterior postoperative pelvic radiograph showing a good positioning of the
prosthetic implant with no signs of fracture.
The postoperative course was uneventful, without thermal rises and with good recovery
of the ROM. Antiembolism prophylaxis was administered with 4,000 I.U. of low-molecular-weight
heparin for 40 days following our standard protocol. Patients with CIPA reported a
higher risk of infection due to a radical shift in body temperature, mainly dictated
by environmental temperature, a feature that is only partially explained by the inability
to sweat due to defective sweat gland innervation. For this reason,[10] we opted for a prolonged double antibiotic prophylaxis with a third generation cephalosporin
and a fluoroquinolone for 6 days after the operation. No complications to the surgical
wound were observed. The rehabilitation had a regular course with immediate weight
bearing allowed. Monthly postoperative clinical checks were scheduled for the first
year. At the last examination, 1 year after the THA procedure, X-rays did not show
periprosthetic fractures or implant mobilization ([Fig. 4]) and the HHS was 93. Improvement in HSS was due only to the “function” and the “deformity”
items, pain being an irrelevant item in patients affected by CIPA.
Fig. 4 Anteroposterior radiograph 1 year after surgery shows well-fixed components, no osteolysis,
or mobilization of the prosthesis.
Discussion
CIPA is a rare disorder characterized by autonomic and sensory nerves malfunction
with insensitivity to both deep and superficial painful stimuli, inability to sweat
and produce tears, and mild to moderate mental retardation. From an orthopaedic point
of view, this condition puts the patient at risk for inveterate bone and joint fractures
that could ultimately act as a predisposing factor for the development of osteomyelitis.
The later a fracture is diagnosed, the bigger the damage to bone stock and surrounding
tissues will be, making the surgical managing more challenging. Thus, strict and careful
physical examination should be performed periodically.
Recent studies have showed that although skeletal complications are more common in
the lower limbs, almost all bones and joints may be affected. Szöke in 1996[11] showed that 26% of patients with CIPA presented hip disorders, and these data were
confirmed by Bar-On et al[12] who noted a high incidence of fractures of the lower limbs in patients with CIPA.
Fractures occurred in the early years of life due to the high activity. Another important
issue related to CIPA is the risk of dislocations and infections that are not related
with increasing age.[11]
[12]
In our case report, we faced an inveterate femoral neck fracture with severe head
resorption that despite the young age of the patient made mandatory the implant of
a hip prosthesis. To our knowledge, Erdil et al[13] published the only case of a THA implanted in a patient with CIPA. The authors implanted
a hip prosthesis in a 37-year-old Caucasian female patient using a press-fit implant
due to the young age of the patient. They allowed walking with crutches at 2 days
postoperatively and followed their standard antibiotic and antiembolism protocol,
reporting no complications at 6 months of follow-up.
In our department, we usually implant press-fit prosthesis in young and active people,
but in this case, the osteoporosis, preoperative capsular stretching, and patient's
uncertainty in weight-bearing control in the postoperative period due to the absence
of pain as a regulatory mechanism were the principal reasons for choosing a cemented
implant with a double mobility cup. Furthermore, cemented implant allowed immediate
full weight bearing, thus reducing the risk of pressure ulcers of the skin derived
from lying on bed. Finally, the use of a cemented implant allowed us to reduce the
risk of aseptic loosening or fracture that would have been misunderstood due to the
pathology of the patient.
Limitations to our case report included the limited follow-up and the absence of a
functional evaluation, such as computed pre- and postoperative gait analysis.
