Expanding the clinical and immunological phenotype of prolidase deficiency: A case report.

Prolidase deficiency (PD) is a rare autosomal recessive disorder associated with recurrent infections, immune dysregulation, and autoimmunity. PD is characterized by persistent dermatitis, skin fragility, and non-healing ulcerations on the lower limbs as its main dermatologic characteristics. Herein, we report a boy with PD due to a novel variant in PEPD who had abnormal facies, cognitive impairment, corneal opacity, recurrent infections, and persistent non-healing leg ulcers. Th17 lymphocyte counts and phosphorylated-STAT5 expression following IL-2 stimulation were reduced in our patient as compared to healthy control.

Rituximab to treat prolidase deficiency due to a novel pathogenic copy number variation in PEPD.

Prolidase deficiency (PD) is a rare autosomal recessive inborn error of immunity caused by biallelic homozygous or compound heterozygous loss-of-function mutations in PEPD, the gene that encodes prolidase. PD typically manifests with variable dysmorphic features, chronic cutaneous ulcers, recurrent infections and autoimmune features, including systemic lupus erythematosus. So far, there is no consensus regarding treatment of PD and its autoimmune manifestations. Here, we present a 28-year-old female patient with PD due to a novel homozygous intragenic deletion in PEPD, diagnosed at the age of 6 years and 7 months with an undifferentiated connective tissue disease that, apart from its very early onset, would be consistent with the diagnosis of Sjögren's syndrome. Steroids and diverse conventional synthetic disease-modifying antirheumatic drugs failed to control PD-associated vasculitis and mucocutaneous ulcerations and led to infectious complications, including cytomegalovirus colitis. Introduction of rituximab (RTX) treatment in this patient led to sustained recession of mucocutaneous ulceration, enabling tapering of steroids. High interleukin-1ß (IL-1ß) production by this patient's monocytes, together with the detection of both IL-1ß and interleukin-18 (IL-18) in her serum, suggest enhanced inflammasome activation in PD, whereas the therapeutic efficacy of RTX implies a role for CD20 positive B cells in the complex immunopathogenesis of PD.

Obstinate leg ulceration secondary to prolidase deficiency, treated with 5% topical proline.

Prolidase deficiency is a rare cause of chronic ulceration with less than 100 reported cases in the literature. This article highlights to clinicians the features of this uncommon genodermatosis, the challenge of diagnosis, and treatment options.

Prolidase Deficiency Causing Recalcitrant Leg Ulcerations in Siblings.

ABSTRACT: Prolidase deficiency (PD) is a rare autosomal recessive genodermatosis with variable clinical manifestations. It results from a mutation in the peptidase-D gene that leads to abnormal activity of the prolidase enzyme, an important player in collagen catabolism. The authors report the case of two siblings presenting with dysmorphic features, disturbed blood panel, and recalcitrant leg ulcerations of several years' duration. Sequencing of the 15 exons and of the intron/exon junction regions of the peptidase-D gene revealed the presence of a homozygous pathogenic variant c.549-1G > A. An ointment with 5% proline and 5% glycine was compounded, and the patients were instructed to apply it once daily. A follow-up visit after 8 months revealed partial improvement of the ulcerations starting from the third month of treatment. These authors hope this case report sheds light on this disease and recommend it be incorporated into the differential diagnoses of chronic leg ulcerations, particularly those starting at a young age.

Topical tacrolimus therapy in the management of lower extremity ulcers due to prolidase deficiency.

Prolidase deficiency is a rare autosomal recessive disorder characterized by cutaneous ulcers, facial dysmorphism, recurrent infections, and intellectual disability. We report a unique case of a 6-year-old boy with prolidase deficiency and Crohn's disease who presented with lower extremity ulcers. Cutaneous ulcers due to prolidase deficiency are historically resistant to treatment, and we report success with the novel use of topical tacrolimus.

Solitary Mastocytoma of the Eyelid in an Adult Patient With Prolidase Deficiency.

Prolidase deficiency and solitary mastocytoma of the eyelid are both exceedingly rare. Prolidase deficiency is an inherited connective tissue disorder that has systemic sequelae, such as intractable skin ulceration, poor wound healing, recurrent infections, and intellectual impairment. Cutaneous mastocytoma is an isolated, aberrant cutaneous aggregation of mast cells. A case of an adult with severe prolidase deficiency who developed cutaneous mastocytoma of the eyelid was presented. To the authors' knowledge, adult-onset solitary mastocytoma of the eyelid has never been reported previously.

Lupus eritematoso sistémico: ¿es una sola enfermedad? / Systemic lupus erythematosus: is it one disease?

El lupus eritematoso sistémico (LES) es una enfermedad multisistémica poseedora de una gran variedad de presentaciones clínicas. Se han descrito enfermedades monogénicas que predisponen la aparición de LES. Como ejemplos tenemos a los defectos en los genes reguladores de la expresión de interferón alfa o a nivel del complemento, que presentan comportamientos clínicos particulares. Estos defectos presentan una presentación y severidad distintas, por lo que se puede argumentar que el lupus no es una sola enfermedad sino varias. El tratamiento se podría individualizar dependiendo del defecto subyacente que genere el subtipo de lupus (AU)

Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease (AU)

Pulmonary manifestations of prolidase deficiency.

BACKGROUND: Prolidase deficiency is a rare autosomal recessive disease, in which pulmonary manifestations have been sporadically reported. AIMS: We have encountered two patients who presented with severe pulmonary cystic lesions leading to respiratory failure. This led us to retrospectively evaluate pulmonary involvement in patients with prolidase deficiency treated in our hospital. RESULTS: Of 21 patients (including the 2 mentioned above), 12 had a history of recurrent pulmonary infections and 10 were diagnosed as having chronic lung disease. Of seven chest CT scans performed, four patients had subpleural cysts, two patients had bronchiectatic changes, and one had diffused ground glass attenuation and minor linear atelectasis. Three patients died, with all deaths being attributed to respiratory insufficiency. CONCLUSIONS: Prolidase deficiency is frequently associated with various pulmonary manifestations, including extensive cystic changes that may be life endangering. The differential diagnosis of bilateral cystic changes should include prolidase deficiency, and pulmonary evaluation should be performed in patients with prolidase deficiency. Pediatr Pulmonol. 2016;51:1229-1233. © 2016 Wiley Periodicals, Inc.

A Rare Cause of Lower Extremity Ulcers: Prolidase Deficiency.

Prolidase deficiency is an autosomal recessive disorder, which is associated with chronic skin ulcers, a characteristic facial appearance, mental retardation, and recurrent infections. This study describes 4 patients with recurrent leg ulcerations and abnormal facies who were first clinically suspected of prolidase deficiency and then biochemically confirmed. Two siblings and 2 other patients were admitted to our clinic at different times, and they had some common features such as chronic leg and foot ulcers recalcitrant to treatment, consanguineous parents, facial dysmorphism, mental retardation, and widespread telangiectasias. Physical examination and detection of low prolidase level in blood finally led us to the diagnose of ulcers secondary to prolidase deficiency. Prolidase deficiency is a rare genodermatosis and must be considered in the differential diagnosis of recurrent leg and foot ulcers that develop at an early age.

Shock séptico de origen cutáneo: déficit de prolidasa / Septic shock originating with a skin infection in a patient with prolidase deficiency

No disponible

INFLAMMATORY BOWEL DISEASE-LIKE PHENOTYPE IN A YOUNG GIRL WITH PROLIDASE DEFICIENCY: A NEW SPECTRUM OF CLINICAL MANIFESTATION.

Prolidase deficiency (PD) is an inherited disorder associated with cutaneous ulcers, intellectual disability, unusual facial appearance, skeletal deformities, hematological anomalies, splenomegaly, and chronic infections. We report a girl with PD who presented with early inflammatory bowel disease (IBD). A 2-month-old girl with a dysmorphic face presented with recurrent respiratory tract infections, vomiting, diarrhea and hepatosplenomegaly. She had steatorrhea, abnormal liver enzymes, hypergammaglobulinemia, autoantibody positivity and steatohepatitis in liver biopsy. On follow-up, skin lesions, pruritus and developmental delay were added. At the age of 21 months, IBD was diagnosed with persistent diarrhea, fever, hypoalbuminemia, elevated inflammatory markers, fecal leukocytes and aphthous ulcers in colon. Remission was achieved with prednisone and continued with mesalasine. Thrombocytopenia developed after 3 years. Her findings prompted us to further investigations. PD as the underlying molecular cause of the disease was detected by exome sequencing. In conclusion, PD should be considered in the differential diagnosis of some IBD patients.

A case of prolidase deficiency accompanying leg ulcers.

Prolidase deficiency (PD) is a rare autosomal recessive disorder that has symptoms such as skin ulcers, characteristic facies, mental retardation, skeletal deformities, hematological anomalies, splenomegaly, and chronic infections. Deficiency of prolidase leads to the increased excretion of proline in urine, which causes impaired collagen synthesis and delay in wound healing. This case reports a 40-year-old female who has had cutaneous ulcers since the age of 7 years. We also recognized borderline intellectual functioning as well as hematologic abnormalities and splenomegaly. We present this rare case to draw attention to consider prolidase deficiency in the differential diagnosis of leg ulcers.

Prolidase deficiency: dento-facial aspects in a paediatric patient.

BACKGROUND: Prolidase Deficiency (PD) is a rare hereditary disease consisting in developmental delay, mental retardation, facial dysmorphism, splenomegaly, recurrent pulmonary infections and skin lesions. CASE REPORT: The present study reports a case of PD treated in the Paediatric Section of the Department of Dentistry and Surgery at the University of Bari. A special diagnostic and clinical approach to the patient was useful to improve his quality of life and identify some new aspects of this systemic disease. In particular, clinical features never described before are reported: low hair line, decreased osteotendinous reflexes, long upper lip, microrhinia, dentoskeletal Class III, dental age (Proffit) older than chronological age, fusion of 2nd and 3rd cervical vertebrae, incomplete atlanto-occipital fusion.