Method for treating porphyria cutanea tarda

FIELD: medicine, dermatology.

SUBSTANCE: it is suggested to apply quingamin in combination with prednisolone. The latter should be prescribed at its average daily dosages, and quingamin daily dosage should be increased for 120-130 mg every 9-11 d beginning from 120-130 mg to reach 450-500 mg/d. Moreover, course dosage of quingamin corresponds to 15-18 mg. The method decreases toxic reactions to quingamin introduction.

EFFECT: higher efficiency of therapy.

1 cl, 1 ex

 

The method relates to the field of medicine, specifically to dermatology.

A necessary condition for the treatment of late cutaneous porphyrias (PEP) is the elimination of factors causing the progression of disorders of porphyrin metabolism and manifestation of the disease, especially alcoholic excesses, industrial poisons and hepatotoxic drugs. However, for the successful treatment of PEP necessary and pathogenetic therapy. To ensure the control panel utilizes a combination of vitamins, adenosine-5-monophosphate and its analogues, chelating agents (unithiol, Desferal) and chelators (cholestyramine, carbolenum, polifan and others), which are able to bind porphyrins in the gastrointestinal tract and remove them from the body (punks BS // the journal of dermatology. - 1967. No. 4. - 67-70; Porphyria /Kuznetsova I.E., punks BS, Chubarova A.S., etc. M., 1981, s-185).

All of the above treatment methods, providing overall beneficial effect, not stabilize the disturbed metabolism of porphyrins and do not result in stable clinical remission (Idelson LI //Therapeutic archive. - 1987. No. 6. - P.143-150; Krivosheev BN. //Russian journal of skin and venereal diseases. - 1999. No. 2. - P.67-74).

As evidenced by recent publications, the most effective at present, the control panel continues to be offered in the 60-ies of XX century synthetically the antimalarials aminoquinolinic series (Saltzer ET, Redeker A.G., Wilson J.W., L. Beach //Archiv Dermatology Research. - 1968. - Vol. 98. - P. 496-498; Sweeney G.D., S.J. Saunders, Dowdle E.B., L. Eales //British Medical Joumal. - 1965. - Vol.1 - No. 5445. - P. 1281-1285), in particular hingamin (delagil, resochin etc).

Hingamin used in large and in small doses. Regardless of the mode of treatment clinical effect is achieved using hingamina in the course dose 15-18, large doses (500 mg/day) treatment is 3-3,5 months and allows you to get the majority of patients with subcompensated biochemical and prolonged clinical remission. However hingamin and its analogues in high doses natural cause patients specific to PEP toxic reaction aggravation in the form of heavy porphyrin crisis", which in single patients may be accompanied by transient ascites and short-term, but significant liver dysfunction (Redeker A.G., W.B. Reed //Archiv Dermalology. - 1974. - Vol. 110. - P. 819-823; Vogler W.R., Calambos J.T, Okunsky S. //Amer. J. Med. - 1970. - Vol. 87. - P. 261-265).

Although after the reaction exacerbation in patients in the near-and long-term observations there is a clear tendency toward normalization of the functional liver samples and morphological changes of hepatocytes (Tsega E. //Quart. J. Med.-1987.-Vol. 65 (New Series). No. 247. - P. 953-957), however, at present, preference is given to small doses hingamina and its analogues (125 mg twice a week) - the regime of small doses (p is the same total course dose of 15-18 g). This regimen avoids the reaction of deterioration, but to achieve biochemical and clinical effect requires a long time - from 8 to 10 months (Goerz G., Bolsen K, Merk H. //Archiv Dermatology. Res. - 1985. - Vol. 277. - R. 114-117; Malina L. Chlumsky J. //Cs. Dermatol. - 1989. - T. 64. No. 2. - P.88-93).

Patients do not always withstand this mode is designed for long term treatment, which reduces its effectiveness. Offers shorter (from 3 up to 6 months) regimen with a gradual reduction of the intervals between meals aminoquinolinic drugs and increase their dose (Idelson LI //Clinical medicine. - 1980 - No. 5. - P.61-63; Malkinson F.D., Levill L. //Archiv Dermalology. - 1980. - Vol. 116. - P. 1147-1150), as well as recommendations, in order to avoid possible complications, assign hingamin after 3 or 5 repeated bloodletting (Dermatology: an Atlas of reference. /Fitzpatrick T., Johnson, R., Wolff, K., and others - M., 1999. - S-267; Seuberi S., Seuberi A., Stella, A.M. et al.//Z. Hauttkrnkh. - 1990. - Bd. 65. - S. 223-225; Swanberk P.L., J.H. Epstein, Marver H.S. //British Journal Dermatology. - 1977. - Vol. 99. - P. 77-80).

The essence of the proposed method of treatment, the control panel is that hingamin used in combination with prednisolone (combination therapy). Use the same dose rate hingamina (15-18 g). Advantages of the method are that it reduces the time of treatment (6-8 weeks) and at the same time avoids patients, it is giving toxic reactions or reduce the severity of the symptoms to a minimum. Clinical remisse observed within 2-3 years.

The treatment begins with a destination patient prednisolone at a daily dose of 15-20 mg for a period of 13-15 days. 4-5-th day from the beginning of treatment in addition to prednisolone appoint hingamin in a daily dose of 120-130 mg Daily dose hingamina increase every 9-11 days from start of treatment to 120-130 mg, bringing it up to 450-500 mg dose rate hingamina lead up to 15-18 year

Treatment by this method held on 17 patients with the first panel (16 men and 1 woman) aged from 29 to 58 years. Disease duration was varied from 2 months to 12 years (average duration of 2.5±0.9 years). The diagnosis of PCP was confirmed on the basis of typical clinical picture and the results of biochemical studies. Patients spectrophotometric methods was determined by the content of uroporphyrin (UE) and coproporphyrin (KP) in the urine, KP and protoporphyrin (PP) in Calais. Studies were performed before treatment, after 7 days destination hingamina, discharge of patients from hospital and some patients in long-term period of observation.

Systematically abused alcohol 13 of 17 patients. Contact with leaded gasoline, other petroleum products and heavy metals (lead, mercury) had 7 people, had been in regular contact with organic solvents and nitropaints 2 patients and 1 patient runs the aspects of the use of oral contraceptives, containing estrogen. From accompanying diseases 5 patients had alcoholic liver disease (alcoholic hepatitis and alcoholic steatosis), 4 - hypertension stage I and II and 3 patients with chronic obstructive bronchitis.

Treatment all patients were started in the hospital. None of them during the reception hingamina was not observed clinically severe reactions exacerbation. Body temperature remained normal. Patients complained of a violation of the General conditions. Tolerability hingaminom on the proposed modification is estimated by us as satisfactory, although 4 patients in the first 2-4 days after the appointment of the drug occasionally noted intermittent headache and mild abdominal discomfort, loss of appetite, feelings of heaviness in the right hypochondrium, slight nausea and rumbling in the abdomen. Patients were treated in the hospital from 22 to 35 days (average duration 28,6±2.2 days). At the time of discharge they received 375 or 500 mg hingamina per day, and the total dose of the drug were they from 4,125 to 9,125, At discharge, patients were recommended to refuse alcoholic beverages to remain under medical supervision, to continue treatment hingaminom outpatient and bring it to the total dose rate at least up to 15, Each patient received the scheme further therapy in which the days were painted daily dose and timing of completion of treatment.

Main indicators of porphyrin metabolism in 13 patients were identified during treatment in hospital and at 6 - long-term observations. Before treatment, all patients found to have a typical manifest PEP biochemical characteristics: the content of porphyrins in the urine was increased mainly due to the UE, and in Calais dominated fraction of KP. The purpose hingamina was accompanied patients naturally in the treatment of aminoquinolinic drugs dynamics in the content of porphyrins in the urine and feces. By the end of the 1st week after inclusion in the complex therapy hingamina excretion pack of urine was increased to an average of 2.5 times, and the total content of porphyrins in the feces was increased 1.5 times mainly due to the fraction of CP. Avalanche 20-fold increase in the excretion pack with urine that is always logged on the background of clinically severe toxic reactions exacerbation, patients were not observed. At discharge patients from the hospital (by the end of the 4th week of treatment hingaminom) level of porphyrins in both biosubstrate decreased to the initial values. In conjunction with increased excretion of porphyrins in the urine and an increase in their content in the stool of patients in 3-4 times increased activity of transaminases (Alt and AST) in the serum, which is characteristic of the initial stages of the treatment control panel aminoquinolinic drugs. By the time wipes the patients and from the hospital, the activity of Alt and AST were significantly decreased, but complete stabilization compared with the original data were not observed.

Long-term results for a period of from 1 to 1.5 years traced in 7 patients. In 6 of them stated clinical subcompensated biochemical remission. The contents of the pack and KP in the urine at this stage, although it remained higher than normal values, but compared to baseline levels significantly (p<0.001) and decreased. These patients comply with recommended treatment. The relapse of the disease after 6 months occurred in 1 patient, who immediately after discharge receiving hingamina stopped and brought the volume of therapy to the required volume. As an illustration, here is one of our observations.

Patient J. 53 years, driver. Was admitted to the hospital with the regular recurrence of the control panel. The first symptoms appeared 3 years ago. Relapses occur annually in late may - early June. Smoke, consume alcohol frequently. Constantly for many years in contact with leaded gasoline. Family history without features. Not systematically treated.

State upon receipt of satisfactory. Complains about the eruption of bubbles and light the vulnerability of the skin on the face and back surfaces of the brushes. Constantly worried about the cough with a moderate amount of sputum. The rhythmic heart sounds slightly muffled. Blood pressure is 125/80 mm Hg, pulse 78 / min. In the lungs - dry items the dust. The liver acts from under the costal arch by 1.5-2 cm; the top of her smooth, slightly sensitive. Skin of dorsal surfaces of hands vesicles with serous-hemorrhagic content and numerous erosion, some of which are covered with brownish crusts. When the mechanical impact of the epidermis easily exfoliate. On the face of the earthy bronze pigmentation, single erosion, covered with crusts. On the anterior and lateral surfaces of the neck symptoms "lemon skin" and "glow".

Laboratory studies on admission. A General analysis of urine and blood without deviation from the norm. Total bilirubin 16.4 µmol/l, direct-2.1 mmol/l; AST 1.0 µmol/l, Alat 0.8 µmol/l; alkaline phosphatase 0.7 µmol/l; iron serum 24.5 μmol/l; gammaglutamyl-transpeptidase 1.8 µmol/L. Markers of viral hepatitis b and C was not detected. The content pack in the urine 2328 nmol/day and KP 317 nmol/day. On ultrasound the size of the liver is enlarged, the structure is non-homogeneous, granular, the diameter of the portal vein 11 mm, splenic vein 8 mm Spleen not enlarged. Conclusion: signs of fatty liver. Conducted esophagogastroduodenoscopy: erosive-ulcerative lesions of the mucous membrane of the esophagus, stomach and duodenum was not found.

Clinical diagnosis: the first panel, acute stage, alcoholic steatohepatitis, chronic obstruct wny bronchitis.

The treatment according to the proposed method. Prednisolone 20 mg daily course of 14 days. On the 4th day in addition to prednisolone assigned hingamin at a dose of 125 mg On the 11th day from the beginning of treatment the daily dose hingamina doubled. Thereafter every 10 days daily dose hingamina was increased to 125 mg to achieve 500 mg, and this dose, the patient was taken to achieve a total dose of hingamina not less than 15,

After 2 days of admission hingamina the patient has no appetite, he began to notice a feeling of heaviness in the right hypochondrium and easy podtashnivaet. 3-4 days later these phenomena were further treatment of the patient endured well. The content of porphyrins in the urine (7 days after the appointment hingamina): UE 5272 nmol/day and KP 696 nmol/day; Alat 4.9 µmol/l and AST 4.3 µmol/L.

The patient was discharged on 33 days in good condition for outpatient monitoring and further treatment. Before discharge of the contents of porphyrins in the urine: UE 1788 nmol/day and KP 346 nmol/day. Alt in the serum of 2.7 µmol/l, AST 2.6 µmol/day. Daily dose hingamina when the extract 500 mg Treatment hingaminom finished 13 days after discharge (course of treatment was 6 weeks and 4 days). Additionally surveyed 3 months after discharge. The patient is maintained clinical remission. Alcohol consumption has reduced, but not completely abandoned. Soda is the content pack in the urine 237 nmol/d & CP 178 nmol/day.

1. Treatment of late cutaneous porphyrias, including the application of hingamina, characterized in that hingamin used in combination with prednisolone.

2. The method according to claim 1, characterized in that the prednisone is prescribed for 3-4 days before hingamina a period of 13-15 days, hingamin administered in a daily dose of 120-130 mg, increasing it every 9-11 days from start of treatment to 120-130 mg and bringing daily dose hingamina to 450-500 mg, and exchange - 15-18,



 

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