Crural Ulcers at Lower Limbs: Acquired or Genetic Pathology
Crural Ulcers at Lower Limbs: Acquired or Genetic Pathology
The authors report a case of a 50-year-old man with bilateral, wide, crural ulcers of 1-year duration on the lower limbs. The patient experienced 3 transient ischemic attacks (TIAs), and instrumental exams revealed thrombotic events involving the kidney, lung, and central nervous system (CNS). The authors performed a thrombophilic screening, which indicated altered concentrations of C and S proteins and antithrombin III (AT III) and a single-base mutation (C677T) at the methylene tetrahydrofolate reductase gene (MTHFR). Methylene tetrahydrofolate reductase gene mutation may be associated with a coagulation system disorder. These data suggest that the MTHFR mutation may be responsible for cutaneous ulcer pathogenesis.
A 50-year-old man presented with bilateral, wide, painless, crural ulcers of 1-year duration on his lower legs. In addition to arterial hypertension, chronic glomerulonephritis, and chronic obstructive bronchopneumopathy (COBP), the patient experienced 3 transient ischemic attacks (TIAs). There was no family history of thromboembolic disease. Cutaneous ulcers were characterized by oval shape, rolled borders, and sticky, suppurative coating with abundant granulation tissue (Figure 1).
(Enlarge Image)
Cutaneous ulcers on both legs characterized by rolled borders and sticky suppurative coating.
Laboratory and immunological examinations revealed azotemia 24 mg/dL (normal 9-23 mg/dL); creatinine 1.9 mg/dL (normal 0.7-1.5 mg/dL); immunoglobulin E (IgE) 400 Ul/mL (normal < 160 Ul/mL); C4 15 mg/dL (normal 16-38 mg/dL); alfa-1-acid glycoprotein 146 mg/dL (normal < 140 mg/dL); and antistreptolysin titer (AST) 500 UAS/mL (normal < 250 UAS/mL). C reactive protein (CRP) was positive. Additional results revealed CD3 78.3% (normal 59-76%); CD4 54.7% (normal 40-53%); CD56 (NK) 8.8% (normal 1-7%); CD2 82.9% (normal 60-80%); and CD19 2.1% (normal 4-12%). NK activity was 24% (100:1), 12.4% (50:1), 9.6% (25:1), and 5.4% (12.5:1). Antibody screening (ANA, ENA, ANCA, anti-MPO, anti-PR3) and viral and treponemal markers (HIV, CMV, HbsAg, HCV, TPHA, RPR) were negative.
Several skin biopsies of the ulcers showed the presence of granulation tissue with reactive polymorphous inflammation (Figures 2 and 3).
(Enlarge Image)
Granulation tissue associated with reactive polymorphous inflammation. (Hematoxylin-eosin [H&E] stain; original magnification x40)
(Enlarge Image)
Inflammatory infiltrate of the dermis. (H&E stain; original magnification x100)
An echocardiogram showed mild mitral/aortic insufficiency; total body and cranial computed tomography (CT) showed kidney size reduction, pleural deposits, and the presence of sharply delimited areas of white matter at the frontoparietal region -- signs of ischemic events.
Therefore, the authors performed a thrombophilic screening to measure antithrombin (AT) III, S and C proteins, and Leiden and von Willebrand (VW) factor serum levels. Additionally, the authors studied the genes frequently involved in coagulation disorders that codified for:
These analyses showed a reduction of AT III and S and C protein serum levels and a single-base mutation (C677T) at MTHFR in heterozygous state.
Methylene tetrahydrofolate reductase enzyme is involved in methionine metabolism regulation via vitamins B6 and B12 and folic acid as cofactors. The altered thermolabile protein, codified by the mutated MTHFR gene, could lead to hyperhomocysteinemia, which is a high risk factor for coagulation disorders. In this patient, homocysteine serum level was 11.86 µmol/L (normal < 15.00 µmol/L); cystinuria was negative.
On the basis of these data, the authors applied the following therapy:
Aside from chlorate solution, no topical therapy was administered.
After a year, the authors observed a decrease of exudation and a reduction in ulcer size (Figures 4 and 5). The encouraging evolution of clinical aspects and the recently tested normal AT III and S and C protein serum levels confirm the efficacy of the therapy applied.
(Enlarge Image)
Reduction of cutaneous ulcers after 6 months of therapy.
(Enlarge Image)
Increasing of epithelial tissue becomes more evident after 12 months of therapy.
The authors report a case of a 50-year-old man with bilateral, wide, crural ulcers of 1-year duration on the lower limbs. The patient experienced 3 transient ischemic attacks (TIAs), and instrumental exams revealed thrombotic events involving the kidney, lung, and central nervous system (CNS). The authors performed a thrombophilic screening, which indicated altered concentrations of C and S proteins and antithrombin III (AT III) and a single-base mutation (C677T) at the methylene tetrahydrofolate reductase gene (MTHFR). Methylene tetrahydrofolate reductase gene mutation may be associated with a coagulation system disorder. These data suggest that the MTHFR mutation may be responsible for cutaneous ulcer pathogenesis.
A 50-year-old man presented with bilateral, wide, painless, crural ulcers of 1-year duration on his lower legs. In addition to arterial hypertension, chronic glomerulonephritis, and chronic obstructive bronchopneumopathy (COBP), the patient experienced 3 transient ischemic attacks (TIAs). There was no family history of thromboembolic disease. Cutaneous ulcers were characterized by oval shape, rolled borders, and sticky, suppurative coating with abundant granulation tissue (Figure 1).
(Enlarge Image)
Cutaneous ulcers on both legs characterized by rolled borders and sticky suppurative coating.
Laboratory and immunological examinations revealed azotemia 24 mg/dL (normal 9-23 mg/dL); creatinine 1.9 mg/dL (normal 0.7-1.5 mg/dL); immunoglobulin E (IgE) 400 Ul/mL (normal < 160 Ul/mL); C4 15 mg/dL (normal 16-38 mg/dL); alfa-1-acid glycoprotein 146 mg/dL (normal < 140 mg/dL); and antistreptolysin titer (AST) 500 UAS/mL (normal < 250 UAS/mL). C reactive protein (CRP) was positive. Additional results revealed CD3 78.3% (normal 59-76%); CD4 54.7% (normal 40-53%); CD56 (NK) 8.8% (normal 1-7%); CD2 82.9% (normal 60-80%); and CD19 2.1% (normal 4-12%). NK activity was 24% (100:1), 12.4% (50:1), 9.6% (25:1), and 5.4% (12.5:1). Antibody screening (ANA, ENA, ANCA, anti-MPO, anti-PR3) and viral and treponemal markers (HIV, CMV, HbsAg, HCV, TPHA, RPR) were negative.
Several skin biopsies of the ulcers showed the presence of granulation tissue with reactive polymorphous inflammation (Figures 2 and 3).
(Enlarge Image)
Granulation tissue associated with reactive polymorphous inflammation. (Hematoxylin-eosin [H&E] stain; original magnification x40)
(Enlarge Image)
Inflammatory infiltrate of the dermis. (H&E stain; original magnification x100)
An echocardiogram showed mild mitral/aortic insufficiency; total body and cranial computed tomography (CT) showed kidney size reduction, pleural deposits, and the presence of sharply delimited areas of white matter at the frontoparietal region -- signs of ischemic events.
Therefore, the authors performed a thrombophilic screening to measure antithrombin (AT) III, S and C proteins, and Leiden and von Willebrand (VW) factor serum levels. Additionally, the authors studied the genes frequently involved in coagulation disorders that codified for:
AT III
C protein
S protein
Leiden V factor
Prothrombin gene
5-10 methylene tetrahydrofolate reductase (MTHFR)
Cystathionine ß synthetase.
These analyses showed a reduction of AT III and S and C protein serum levels and a single-base mutation (C677T) at MTHFR in heterozygous state.
Methylene tetrahydrofolate reductase enzyme is involved in methionine metabolism regulation via vitamins B6 and B12 and folic acid as cofactors. The altered thermolabile protein, codified by the mutated MTHFR gene, could lead to hyperhomocysteinemia, which is a high risk factor for coagulation disorders. In this patient, homocysteine serum level was 11.86 µmol/L (normal < 15.00 µmol/L); cystinuria was negative.
On the basis of these data, the authors applied the following therapy:
Folic acid 5 mg/die
Vitamin B6 750 mg/die, vitamin B12 1.5 mg/die, and vitamin B1 750 mg/die
Acetylsalicylic acid 100 mg/die.
Aside from chlorate solution, no topical therapy was administered.
After a year, the authors observed a decrease of exudation and a reduction in ulcer size (Figures 4 and 5). The encouraging evolution of clinical aspects and the recently tested normal AT III and S and C protein serum levels confirm the efficacy of the therapy applied.
(Enlarge Image)
Reduction of cutaneous ulcers after 6 months of therapy.
(Enlarge Image)
Increasing of epithelial tissue becomes more evident after 12 months of therapy.
Source...