Keywords
complex regional pain syndrome - snake bite - MRI - bone scan - SPECT/CT
Introduction
Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by
Hyperalgesia and allodynia, typically affecting the extremities.[1] While the exact pathophysiology of CRPS remains under investigation, it is believed
to involve dysfunction of both the central and peripheral nervous systems.[2] It remains unclear whether CRPS is primarily triggered by nerve damage or soft tissue
injury. Recent research suggests that multiple mechanisms may contribute to its development.[3] CRPS following a snake bite is extremely rare, with only two cases reported globally.[4]
[5] de Mos et al. proposed that dysfunction in the autonomic and somatic nervous systems,
along with neurogenic inflammation, tissue hypoxia, and psychological factors, may
all play a role in CRPS pathogenesis.[6] The inflammation and edema resulting from a snake bite could potentially lead to
the onset of CRPS.[7] Diagnosing CRPS is challenging and relies on evolving clinical criteria. Over the
past two decades, these criteria have undergone several revisions. While laboratory
tests and imaging techniques such as plain film radiography, magnetic resonance imaging
(MRI), and triple-phase bone scan can aid in diagnosis, no definitive diagnostic standard
exists, making CRPS a complex clinical entity to identify.[8]
[9]
[10]
[11] In particular, the use of three-phase bone scintigraphy with SPECT/CT adds significant
diagnostic value. It enables early detection of regional blood flow changes and periosteal
reaction, as well as provides anatomical localization, which helps differentiate CRPS
from osteomyelitis or other inflammatory conditions. This hybrid imaging modality
is especially valuable when clinical findings are ambiguous or overlap with other
musculoskeletal disorders.
Case Report
A 47-year-old previously healthy male presented following a snake bite in October
2024, which occurred on the dorsum of his left foot. Initial symptoms included severe
pain, swelling, erythema, and the formation of large bullae. He received prompt medical
attention, including administration of antivenom and admission to the intensive care
unit for close monitoring. Despite appropriate treatment, the patient continued to
experience unresolved pain and swelling in the affected limb as shown in [Fig. 1A]. Over time, he reported worsening localized pain, warmth, and hypersensitivity,
particularly during movement, no significant systemic symptoms were noted.
Fig. 1 (A) Clinical image showing skin changes and erythema. (B) Axial T2 MRI (January 2025) reveals soft tissue edema and fluid collection suggestive
of cellulitis and abscess. (C) Follow-up MRI axial T2 (April 2025) shows persistent inflammation with new fat necrosis
and deeper extension. MRI, magnetic resonance imaging.
Management and Imaging
The patient's physical examination revealed signs of local inflammation and tenderness,
raising concerns for cellulitis or abscess formation. An MRI was performed in January
2025, which showed diffuse subcutaneous soft tissue edema at the dorsum of the left
foot with fluid collection as shown in [Fig. 1B]. There was a small soft tissue lesion (11 × 15 mm) at the first metatarsophalangeal
joint space. The radiological impression suggested cellulitis with abscess formation
and a potential diagnosis of fibromatosis. No evidence of fracture or joint derangement
was identified. A follow-up MRI was conducted in April 2025 to assess for evolving
pathology. The MRI revealed near-stable soft tissue signal changes, but with newly
noted areas of fat necrosis, persistent irregular enhancement, and deeper extension
of inflammation into the plantar aspect of the foot as shown in [Fig. 1C]. Signs of evolving periostitis throughout the metatarsal heads and necks were noted,
along with synovial enhancement and joint effusion at the metatarsophalangeal joints.
The radiologist recommended correlation with bone scan to evaluate for possible osteomyelitis.
Following the last MRI in April 2025, a triple-phase bone scintigraphy was performed
using 99mTc-HDP as per standard protocol.[12] Early-phase dynamic and blood pool scintigraphy revealed increased perfusion and
hyperemia predominantly involving the knee and the dorsum of the left foot, indicating
active inflammatory changes. The activity appeared diffusely distributed across multiple
joint regions, suggesting an extensive inflammatory process. Delayed whole-body and
SPECT/CT imaging of the feet showed diffuse peri-articular and articular tracer uptake
in multiple joints of the left foot, specifically involving the left tibiotalar, tibiofibular,
talonavicular, and various proximal and distal tarsal and metatarsal joints, with
notable uptake at the first metatarsophalangeal joint, consistent with periostitis
and elevated osteoblastic activity ([Fig. 2]). Corresponding CT images revealed fat stranding and soft tissue edema localized
to the left foot, further supporting an inflammatory etiology ([Fig. 3]). Hybrid SPECT/CT imaging allowed precise anatomical localization of radiotracer
uptake to bony structures and helped exclude abscess or osteolytic lesions, thereby
enhancing diagnostic confidence. These findings collectively raise strong suspicion
CRPS, affecting the left foot.
Fig. 2 Bone scintigraphy. (A) Whole-body blood pool and delayed phase images demonstrating areas of increased
tracer uptake. (B) Static blood pool and delayed images focusing on the anterior foot and left knee.
Notably, the focal uptake in the medial tibial plateau of the left knee may suggest
underlying arthritis rather than CRPS, which typically presents as a more diffuse
periarticular uptake pattern. CRPS, complex regional pain syndrome.
Fig. 3 SPECT/CT imaging of the left foot. The figure includes CT images, nuclear medicine
images, and fused hybrid SPECT/CT images, demonstrating localized tracer uptake and
corresponding anatomical abnormalities in the affected region. CT, computed tomography;
SPECT, single-photon emission computed tomography.
Discussion
CRPS following a snakebite is an extremely rare clinical entity, with very few cases
reported in the literature. In the case described by Pachowicz et al.,[13] a patient developed CRPS in the same limb that had sustained a viper bite; however,
bone scintigraphy was performed 2 years after the envenomation. Although the viper
species was not identified and a direct causal relationship could not be definitively
established, the authors proposed that the envenomation may have acted as a predisposing
or facilitating factor by triggering a delayed inflammatory and autonomic response.
In contrast, in our case, bone scintigraphy was performed 6 months after the snake
bite, allowing for an earlier diagnosis of CRPS and strengthening the link between
the envenomation and the onset of the syndrome.
CRPS typically progresses through three clinical phases. The first, known as the hyperemic
phase, is marked by symptoms such as pain, tenderness, swelling (edema), increased
skin temperature, excessive sweating, redness, and accelerated growth of hair and
nails. The second phase, referred to as the dystrophic phase, usually emerges after
several weeks and is characterized by persistent burning pain, hyperalgesia, cold
and pale skin, hair loss, cyanosis, and trophic changes in the nails. In the third
and final phase, the atrophic phase, which develops after several months, patients
often experience muscle atrophy, joint contractures, and significant movement limitations.[2] Temperature asymmetry is a hallmark of CRPS, and thermography can serve as a useful
diagnostic tool. A temperature difference of at least 1°C between affected and unaffected
limbs is generally considered clinically significant.[14] In this case, it is consistent with the second phase of CRPS ([Fig. 1A]). The envenomation appears to have triggered a cascade of local inflammation and
possible autonomic dysregulation, culminating in chronic pain, edema, and tissue changes.[2] The delayed yet progressive onset of symptoms, including swelling, hypersensitivity,
and functional impairment in the absence of overt infection, supports this rare diagnosis.
Imaging modalities played a critical role in confirming the diagnosis and excluding
other potential causes. Triple-phase bone scan with SPECT/CT was particularly pivotal
in detecting early alterations in bone metabolism that were not visible on conventional
radiography.[10] This imaging modality confirmed active inflammatory involvement suggestive of CRPS
and helped differentiate it from other conditions such as osteomyelitis or soft tissue
infection. Furthermore, the bone scan supported MRI findings of evolving periostitis
without cortical bone destruction, allowing for the confident exclusion of aggressive
infectious processes.
The diagnosis of CRPS was made based on the Budapest criteria established by the International
Association for the Study of Pain.[15] This was supported by the patient's disproportionate pain, sensory disturbances,
vasomotor changes, edema, and the exclusion of alternative diagnoses through clinical
assessment and multimodal imaging. This combination of functional and structural imaging
provided valuable insight into the underlying neuroinflammatory changes, thereby guiding
appropriate management. This case contributes to the limited body of literature documenting
CRPS following snakebite envenomation and highlights the importance of considering
this diagnosis in patients with persistent pain and swelling postenvenomation. Early
recognition and the use of comprehensive imaging strategies, including triple-phase
bone scan with SPECT/CT and MRI, are essential for accurate diagnosis and tailored
therapeutic intervention.
Conclusion
This case underscores the rare occurrence of CRPS following a snake bite, the patient
had ongoing pain and swelling without signs of infection or fracture, making diagnosis
difficult. Imaging with MRI and triple-phase bone scan with SPECT/CT helped detect
early bone changes and rule out other conditions like infection. This highlights the
importance of considering CRPS in similar cases and using advanced imaging to guide
early and proper treatment.
