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Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema.

Blanco I, Lara B, de Serres F - Orphanet J Rare Dis (2011)

Bottom Line: However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma.Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection.These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Research Office (OIB-FICYT), Rosal, 7. 33009 Oviedo, Principality of Asturias, Spain. ignablanco@yahoo.com

ABSTRACT
Up to now alpha 1-antitrypsin (AAT) augmentation therapy has been approved only for commercial use in selected adults with severe AAT deficiency-related pulmonary emphysema (i.e. PI*ZZ genotypes as well as combinations of Z, rare and alleles expressing AAT serum concentrations <11 μmol/L). However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma. Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection. These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema. The aim of the present study is to compile and analyze both clinical and histological features of the aforementioned published case studies and reports where AAT augmentation therapy was used for conditions other than pulmonary emphysema. Particularly, our research refers to ten case reports and two clinical trials on AAT augmentation therapy in patients with both AAT deficiency and, at least, one of the following diseases: fibromyalgia, vasculitis, panniculitis and bronchial asthma. In all the cases, AAT was successfully applied whereas previous maximal conventional therapies had failed. In conclusion, laboratory studies in animals and humans as well as larger clinical trials should be, thus, performed in order to determine both the strong clinical efficacy and security of AAT in the treatment of conditions other than pulmonary emphysema.

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Related in: MedlinePlus

Timeline of clinical events in a case of leukocytoclastic vasculitis related to ZZ alpha-1-antitrypsin deficiency. AAT: alpha-1-antitrypsin.
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Figure 1: Timeline of clinical events in a case of leukocytoclastic vasculitis related to ZZ alpha-1-antitrypsin deficiency. AAT: alpha-1-antitrypsin.

Mentions: In 1995 Dowd et al (University of Louisville School of Medicine, Louisville, Kentucky) reported a case of to "a 49-year-old man, with a PI*ZZ genotype and AAT serum of 24 mg/d, suffering from extensive cutaneous leukocytoclastic vasculitis, with multiple recurrences partially controlled with colchicine, prednisone, plasma infusions and plasma-exchange therapy" [61]. Authors describe the occurrence of repetitive outbreaks of fever, chills, purpuric papules and nodules in lower extremities, arms, face, trunk, hands and the lateral abdominal wall, provoking large vitiligo areas in elbows, knees, dorsal hand and pretibial surfaces. A biopsy skin sample showed alterations related to leukocytoclastic vasculitis (i.e. inflammatory involvement of medium and small vessels, red blood cell extravasations, edema and clear neutrophilic invasion with leukocytoclasia (disrupted neutrophils). The results of a complete blood cell count, serum multiphasic analysis and urinalysis were normal. Studies with normal or negative findings included assays for antinuclear antibody, antibodies to extractable nuclear antigen, antinuclear DNA, complement levels and hepatitis B surface antigen. The chest roentgenogram was within normal limits as well as pulmonary function tests. Five years later, the patient displayed a "dramatic response after 1 dose of Prolastin® (60/mg/Kg), with improvement <6 hrs, and total resolution <48 hrs" and "good control with long-term augmentation therapy (60/mg/Kg)/1-2 weeks" (Figure 1).


Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema.

Blanco I, Lara B, de Serres F - Orphanet J Rare Dis (2011)

Timeline of clinical events in a case of leukocytoclastic vasculitis related to ZZ alpha-1-antitrypsin deficiency. AAT: alpha-1-antitrypsin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094201&req=5

Figure 1: Timeline of clinical events in a case of leukocytoclastic vasculitis related to ZZ alpha-1-antitrypsin deficiency. AAT: alpha-1-antitrypsin.
Mentions: In 1995 Dowd et al (University of Louisville School of Medicine, Louisville, Kentucky) reported a case of to "a 49-year-old man, with a PI*ZZ genotype and AAT serum of 24 mg/d, suffering from extensive cutaneous leukocytoclastic vasculitis, with multiple recurrences partially controlled with colchicine, prednisone, plasma infusions and plasma-exchange therapy" [61]. Authors describe the occurrence of repetitive outbreaks of fever, chills, purpuric papules and nodules in lower extremities, arms, face, trunk, hands and the lateral abdominal wall, provoking large vitiligo areas in elbows, knees, dorsal hand and pretibial surfaces. A biopsy skin sample showed alterations related to leukocytoclastic vasculitis (i.e. inflammatory involvement of medium and small vessels, red blood cell extravasations, edema and clear neutrophilic invasion with leukocytoclasia (disrupted neutrophils). The results of a complete blood cell count, serum multiphasic analysis and urinalysis were normal. Studies with normal or negative findings included assays for antinuclear antibody, antibodies to extractable nuclear antigen, antinuclear DNA, complement levels and hepatitis B surface antigen. The chest roentgenogram was within normal limits as well as pulmonary function tests. Five years later, the patient displayed a "dramatic response after 1 dose of Prolastin® (60/mg/Kg), with improvement <6 hrs, and total resolution <48 hrs" and "good control with long-term augmentation therapy (60/mg/Kg)/1-2 weeks" (Figure 1).

Bottom Line: However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma.Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection.These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Research Office (OIB-FICYT), Rosal, 7. 33009 Oviedo, Principality of Asturias, Spain. ignablanco@yahoo.com

ABSTRACT
Up to now alpha 1-antitrypsin (AAT) augmentation therapy has been approved only for commercial use in selected adults with severe AAT deficiency-related pulmonary emphysema (i.e. PI*ZZ genotypes as well as combinations of Z, rare and alleles expressing AAT serum concentrations <11 μmol/L). However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma. Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection. These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema. The aim of the present study is to compile and analyze both clinical and histological features of the aforementioned published case studies and reports where AAT augmentation therapy was used for conditions other than pulmonary emphysema. Particularly, our research refers to ten case reports and two clinical trials on AAT augmentation therapy in patients with both AAT deficiency and, at least, one of the following diseases: fibromyalgia, vasculitis, panniculitis and bronchial asthma. In all the cases, AAT was successfully applied whereas previous maximal conventional therapies had failed. In conclusion, laboratory studies in animals and humans as well as larger clinical trials should be, thus, performed in order to determine both the strong clinical efficacy and security of AAT in the treatment of conditions other than pulmonary emphysema.

Show MeSH
Related in: MedlinePlus