Acrodystrophic Axonal Polyneuropathy With Celiac Disease

A Case Report

S. N. Bardakov; Minh Duc Tran; S. V. Lapin; A. N. Moshnikova; E. U. Kalinina; E. G. Bogdanova; A. V. Bolekhan; B. L. Gavriluk


J Med Case Reports. 2021;15(615) 

In This Article

Case Presentation

A 41-year-old Ukrainian male [body mass index (BMI) 37.4] presented with complaints of numbness and cramping in the lower extremities, periodic numbness of fingers I–III of both hands, headache, and general weakness that gradually increased over 8 years. Over the past 2 years, the patient noted complete hair loss in the legs, thinning and increased vulnerability of the skin of the lower limbs, and the appearance of limited areas of severe hyperkeratosis on the feet. A callosity on the first toe of the left foot had led to the formation of a long-term, non-healing infected wound that was complicated by gangrene of the terminal phalanx and had led to its amputation.

During examination, the skin of both feet was observed to be thinning with pigmentation, lamellar desquamation, and hyperkeratosis on the plantar surfaces (Figure 1a–d). There were multiple epithelized and unhealed infected wounds on the feet that had developed as a result of microtrauma. The patient also suffered from class II alimentary–constitutional obesity.[30,31]

Figure 1.

Clinical manifestations of acrodystrophic axonal polyneuropathy of 41-year-old patient

A neurological examination revealed impaired exteroception with symmetrical hyperesthesia of the metacarpophalangeal joints, hypoesthesia, anesthesia, and thermal hypesthesia to the level of the middle one-third of the legs by polyneuritic type (Figure 1e). Vibrational sensitivity was reduced to 5 seconds by polyneuritic type. Positional sense was reduced in the distal joints. Tendon reflexes of the lower extremities were weakened. Using the Medical Research Council (MRC) scale, muscle strength in the flexors of the lower legs was reduced by 4 grades, by 5 grades in the extensors, and 5 grades in the distal sections. Before the start of treatment in September 2017, hand dynamometry measured 38 kg and 36 kg on the left and right sides, respectively, which increased to 46 kg and 45 kg following treatment in February 2018. Moderate atrophy and muscle pain in the lower legs and short foot muscles were also found. Sensitive ataxia was noted as well. Autonomic trophic disturbance of the lower extremities was characterized by hyperkeratosis, anhidrosis, and livedo reticularis (Figure 1a).

Despite the absence of complaints from the patient and his relatives, a decrease in cognition was uncovered using the Montreal Cognitive Assessment (MoCa) scale with a score of 18 out of 30, the Mini-Mental State Exam (MMSE) with a score of 23 out of 30, and the Frontal Assessment Battery (FAB) with a score of 13 out of 18. In addition, tests evaluating spatial orientation (the clock drawing task and drawing complex or three-dimensional figures), attention, delayed recall, and phonetic speech activity were found to cause the most difficulties (Figure 1g–k).

Laboratory and Instrumental Tests

To identify the causes of polyneuritis syndrome, we excluded endocrine diseases [normal indicators of insulin, proinsulin, glycated HbA1c, adrenocorticotropic hormone, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4)], infections (cytomegalovirus, Epstein–Barr virus, herpes, and borreliosis), and dysmetabolic origins (vitamin levels for B1, B6, B12, and homocysteine were normal; and amyloid deposition in the subcutaneous fat was absent). Electrophoresis of serum proteins allowed us to exclude the presence of paraprotein with a slight increase in the β1 fraction and hypergammaglobulinemia. Among the possible autoimmune causes, tests for antineutrophil cytoplasmic antibodies (ANCA), antinuclear factor, and extractable nuclear antigen antibodies were negative. An immunoblot of antibodies to gangliosides and onconeural antigens was negative as well. However, recombinant tissue transglutaminase 2 (TG2) IgA antibodies were found to be five times the normal level (90.3 IU/ml, which is normally less than 20 IU/ml). Anti-DGP IgG antibody values were normal (22.8 IU/ml).

Among all the classes of antibodies, only the IgE level was increased at 122 IU/ml.

As an additional source of confirmation for celiac disease, the HLA-DQ2 and HLA-DQ8 alleles were found to be present.

No pathologies or abnormalities were detected following an electrocardiogram, echocardiography, thyroid, abdominal and pelvis ultrasounds, head magnetic resonance imaging (MRI), and chest computed tomography (CT). However, during a nerve conduction study (NCS), signs of gross axonal damage to the motor and sensory fibers of the lower extremities was uncovered, with a complete block at the distal stimulation points of the left tibial and peroneal nerves and signs of secondary demyelination. In the upper limbs, there were signs of moderate axonopathy of the ulnar nerve (Table 1).

To assess the involvement of the gastrointestinal pathological process, a fibroesophagogastroscopy was performed, during which an erythematous gastroduodenopathy was revealed. Biopsies of the gastric and duodenal mucosa were sent for morphological study (Figure 2).

Figure 2.

Pathohistomorphological manifestations the duodenum and the lower one-third of the shins of 41-year-old patient

Morphological analysis of the duodenal mucosa biopsy (Table 2, Figure 2) identified changes (subatrophy of villi in combination with crypt hyperplasia) that correspond to celiac disease according to the Marsh IIIB classification.

Figure 2 shows duodenal mucosa relief, atrophy of the villi, and deepening of the crypts. In Figure 2a, inflammatory infiltration, reactive changes in epithelial cells are presented. In Figure 2b and c, pronounced diffuse lymphoplasmacytic infiltration, an increase of intraepithelial lymphocytes, and a decrease of goblet cells in the surface sections can be seen. Figure 2d and e shows pronounced diffuse lymphoplasmacytic infiltration, with a sharp increase in intraepithelial lymphocytes. In Figure 2f, there are reactive changes in epithelial cells with nucleo- and nucleolomegaly, perinuclear vacuolization, nuclear hyperchromia, and increased mitotic activity. From Figure 2a to f, the plates were stained with hematoxylin and eosin. Examination using direct immunofluorescence (DIF) reaction using antisera (Figure 2g) uncovered C1q deposition (2+) in the papillary dermis, and linear IgA deposition (1+) along the basement membrane of the epidermis (Figure 2h).

Examination of the skin biopsy by DIF using antisera uncovered C1q deposits in the papillary layer of the dermis in the lower one-third of the shin, minor IgA deposits at the intercellular contacts of the epidermis, and linear deposits along the basement membrane of the epidermis. The pattern was similar to linear IgA dermatosis.

Results of Treatment

Multidisciplinary therapy was initiated that included two cycles of five operations of medium-volume membrane plasma exchange, with an exfusion volume of 25–30% of the circulating plasma volume in combination with 1 g of intravenous pulse methylprednisolone. Metabolic therapy included the administration of α-lipoic acid (1200 mg/day); vitamins B6 (50 mg/day), B12 (1000 mg/day), and E (400 units/day); ipidacrine (60 mg/day); sulodexide (500 IU/day); and L-carnitine (3000 mg/day), as well as the initiation of gluten-free diet (GFD).

Eight months following the start of treatment, regression of the clinical symptoms of axonal polyneuropathy and cognitive deficiency was observed (Figure 1f). During the next neurological examination, polyneuritic hypoesthesia was observed at the level of the lower third of the legs with full normalization of thermoception and vibrational sensation. In the upper limbs, hyperesthesia (to the level of the wrist joints) in the distal phalanges occurred, and signs of hyperpathy appeared. The trophic status of the cutaneous lower extremities returned to normal, and previously nonhealing wounds epithelized. Cognitive function was normalized (MMSE score of 28; FAB score of 18; and a MoCA score of 28). The level of recombinant TG2 IgA antibodies decreased to 13.0 IU/ml.