Dyskeratosis congenita with pancytopenia

Dyskeratosis congenita is a rare inherited disorder characterized by skin pigmentation, nail dystrophy, leukoplakia and a variable number of additional features. This paper describes a patient who developed a serious manifestation, pancytopenia, as well as obliterated lacrimal puncta, gingivitis and loss of dermatoglyphics. The tendency to early malignancy is discussed and management by bone marrow transplantation and oral retinoids is proposed.     

X-linked dyskeratosis congenita with pancytopenia

Two maternal male cousins in a Jewish Iraqi kindred were affected with dyskeratosis congenita and had a megaloblastic bone marrow. One cousin had pancytopenia and the other had thrombocytopenia. The kindred displays a deficiency of glucose-6-phosphate dehydrogenase (G6PD) and a beta-thalassemia trait. The following genetic "markers" of the X chromosome were studied: G6PD, the X-linked blood groups Xg, and color vision. Linkage analysis indicated that dyskeratosis, G6PD, and Xg are far apart on the X chromosome. Chromosomal studies showed a 46XY karyotype in both cases; however, nonspecific numerical aberrations and structural abnormalities were found in the first and in the second case, polyploidy was seen in four of 60 cells. The proband's cultured fibroblasts did not show increased susceptibility to malignant transformation by simian virus 40, an oncogenic virus.     

Pulmonary Arteriovenous Malformations in Dyskeratosis Congenita

Pulmonary arteriovenous malformations (PAVMs) are rare lesions known to cause cyanosis due to abnormal communication between the pulmonary arteries and veins. They are commonly seen in association with hereditary hemorrhagic telangiectasia, congenital heart disease, hepatopulmonary syndrome, and portopulmonary shunting, but rarely in patients with dyskeratosis congenita (DC). We describe a patient previously diagnosed with DC confirmed to have microscopic PAVMs after bone marrow transplantation and discuss possible pathogenic mechanisms.     

Dyskeratosis congenita in an adolescent girl with associated choanal atresia

Dyskeratosis congenita is a rare, progressive, degenerative disorder characterized by cutaneous and mucosal involvement in the first decade of life with malignant changes and bone marrow failure in the second and third decades. The primary inheritance pattern is X-linked recessive, with the majority of cases presenting in boys. We report dyskeratosis congenita in an adolescent girl with choanal atresia, a previously unreported association.     

Dyskeratosis Congenita or Chronic Graft-versus-Host Disease? A Diagnostic Dilemma in a Child Eight Years After Bone Marrow Transplantation for Aplastic Anemia

Abstract: A 12-year-old boy had striking reticulate hyper pigmentation of the neck and upper chest, dystrophic nails, patchy alopecia, and a white streak on the buccai mucosa. He was diagnosed as having chronic graft-versus-host disease (GVHD) based on clinical findings, skin biopsy findings, and his history of a bone marrow transplantation for apiastic anemia eight years earlier. Dyskeratosis congenita (DC) was not a diagnostic consideration, although the clinical findings and history of aplastic anemia made it a compelling possibility. This case highlights the clinical similarities between DC and chronic GVHD and the difficulty in arriving at an unequivocal diagnosis.     

Coats plus syndrome (cerebroretinal microangiopathy with calcifications and cysts‐1): A case report

We present a 6‐year‐old girl with skin hyperpigmentation, leukoplakia, and onychodystrophy, the classic mucocutaneous triad usually associated with dyskeratosis congenita. The patient also had premature graying of the hair, bone marrow failure, hepatitis, exudative retinopathy, osteopenia with multiple long bone fractures, and intracranial calcifications and brain cysts. Coats plus syndrome is a rare disease with a clinical and genetic overlap with dyskeratosis congenita. This disease is reviewed, with a focus on the pathogenesis of the genetic anomalies and its background as a telomere biology disorder.     

Dyskeratosis congenita with epidermodysplasia verruciformis of Lewandowsky and Lutz

The case is reported of a 30-year-old man suffering from dyskeratosis congenita with severe pancytopenia, in association with generalized verrucosis. Viral particles were detected electron microscopically. The importance of an impaired immunological state, demonstrated in this case by lymphocyte stimulation and rosette tests, is discussed.     

Dyskeratosis congenita associated with three malignancies

Dyskeratosis congenita is a rare inheritable disorder characterized by abnormalities of the skin, nails and oral mucosa. Aplastic anaemia resulting from bone marrow hypoplasia is a frequent cause of death. Squamous cell carcinoma developing from leukoplakia and visceral malignancies are other complications of the disease. We report here a case of dyskeratosis congenita in a man who developed three neoplasias of different systems over a period of many years. Squamous cell carcinoma and gastric adenocarcinoma manifested 17 years after the man was diagnosed with Hodgkin's disease.     

Hoyeraal–Hreidarsson Syndrome: An Extremely Rare Dyskeratosis Congenita Phenotype

Hoyeraal–Hreidarsson syndrome is a rare telomere biology disorder that is recognized as a severe variant of dyskeratosis congenita. We present a Libyan boy with hematologic and neurologic abnormalities with typical dermatologic manifestations of dyskeratosis congenita. Death usually occurs before the age of 4 years as a result of pancytopenia or malignant transformation of mucocutaneous lesions. The boy presented survived longer than 5 years. Early recognition and appropriate genetic counseling are crucial because of the high mortality of this genetic disorder.     

Dyskeratosis congenita: a literature review

Dyskeratosis congenita is a rare hereditary disease that occurs predominantly in males and manifests clinically as the classic triad of reticulate hyperpigmentation, nail dystrophy and leukoplakia. It increases the risk of malignancy and other potentially lethal complications such as bone marrow failure, lung and liver diseases. Mutations in 19 genes are associated with dyskeratosis congenita, and a fifth of the pathogenic mutations are found in DKC1, the gene coding for dyskerin. This review aims to address the clinical and genetic aspects of the disease.     

Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with Dyskeratosis congenita

Dyskeratosis congenita (DKC) is a rare and fatal congenital syndrome characterized by the triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and the predisposition to bone marrow failure and malignancies. Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita. Here we report mutation analysis of two Chinese pedigrees with dyskeratosis congenita. The 15 coding exons of DKC1 and their flanking regions were amplified from genomic DNA by PCR. DNA sequencing and restriction endonuclease digestion were used for mutation detection. Transition mutation of 1226C-->T (P409L) found in the first pedigree is a novel mutation. In the second pedigree, the proband's mother phenotypically normal carried a de novo transition mutation of 1058C-->T (A353 V) in one allele, and transmitted the mutant allele to her two sons who had typical manifestations of dyskeratosis congenita.     

Two cases of transfusion-associated graft-vs-host disease after open heart surgery.

BACKGROUND--Some cases of blood transfusion-associated (TA) graft-vs-host disease (GVHD) in immunocompetent patients have been reported, but those dermatologic findings were not precisely mentioned. We describe patients with clinicopathologically TA-GVHD and compare TA-GVHD and acute GVHD after bone marrow transplantation. OBSERVATIONS--Two cases of TA-GVHD after open heart surgery are reported. In both immunocompetent patients, severe erythema multiformelike skin rash developed over the entire body, followed by fever, diarrhea, jaundice, transaminitis, pancytopenia, and marrow alpasia approximately 10 days after operation. The rash in one patient changed from erythema multiformelike to toxic epidermal necrolysis at death. Skin biopsy specimens revealed eosinophilic bodies, basal vacuolation, and exocytosis in the epidermis. Eosinophilic bodies tend to appear in the upper epidermis. Immunohistochemistry studies revealed that infiltrating cells were CD4 and CD8. While acute GVHD in immunosuppressed patients who have undergone bone marrow transplantations often shows lichenoid histologic features, TA-GVHD in our patients who were immunocompetent may resemble severe erythema multiforme or toxic epidermal necrolysis. The difference in TA-GVHD may be related to lack of host modification by immunosuppression. CONCLUSIONS--Irradiation of the blood products should be required in open heart surgery, for TA-GVHD in immunocompetent patients is almost always fatal.     

Cutaneous toxoplasmosis

A case of epidermotropic cutaneous toxoplasmosis is reported. The patient, a 53-year-old man with chronic myelogenous leukemia in blast crisis, received a bone marrow allograft but continued to have severe pancytopenia. Numerous diffuse, palpable, purpuric nodules appeared 21 days after the transplant. Organisms were found within the epidermal keratinocytes--both singularly and in cysts. Dermal and neural infiltration was also present. Toxoplasma gondii was identified on the basis of the ultrastructural features of the parasite. Possible sources of infection include reactivation of a previous latent infection, transmission through a bone marrow allograft, or nosocomial acquisition.     

Kaposi's sarcoma and aplastic pancytopenia: simultaneous occurrence in a patient

A 49 year old patient developed simultaneously a histologically verified Kaposi's sarcoma and an idiopathic aplastic pancytopenia. An association of these perhaps virus-induced diseases has not been reported until now. Consequences concerning the diagnostic approach of changes in peripheral blood cells in patients with Kaposi's sarcoma are delineated. Changes in peripheral blood and bone marrow in patients with Kaposi's sarcoma are discussed.     

Aggressive NK-cell leukaemia associated with reactive haemophagocytic syndrome

We report a case of aggressive NK-cell leukaemia associated with reactive haemophagocytic syndrome in a 29-year-old Korean woman who had several small purpuric patches on both thighs. She also had high fever. Laboratory tests revealed pancytopenia and deranged liver function, and atypical lymphocytes containing toxic granules were detected from peripheral blood and bone marrow. The bone marrow examination showed diffuse histiocytic proliferation with several haemophagocytic macrophages, suggesting an associated reactive haemophagocytic syndrome. Skin biopsy from her thigh lesion demonstrated atypical CD56+ lymphoid cellular infiltrates with angiocentric pattern, and in situ hybridization test for Epstein-Barr virus was positive. Although we treated her with chemotherapy, she died 1 month later.     

Acute graft-vs-host disease. Development following autologous and syngeneic bone marrow transplantation

Graft-vs-host disease (GVHD) is a frequent complication of allogeneic bone marrow transplantation but has been infrequently reported following autologous or syngeneic bone marrow transplantation. Ninety-six autologous and 19 syngeneic marrow transplants were performed at our institution between July 1977 and March 1984. We report acute cutaneous GVHD occurring in seven patients who received autologous marrow and two patients who received marrow from an identical twin. All nine patients had clinically detectable eruptions and had skin biopsy specimens with histologic changes of grade 2 acute GVHD. Although most cases were mild and self-limiting, four patients required systemic corticosteroids to treat their disease. Thus, acute cutaneous GVHD was seen in approximately 8% of patients receiving autologous or syngeneic bone marrow transplants at our institution.     

X‐linked dyskeratosis congenita presenting in adulthood with photodamaged skin and epiphora

Dyskeratosis congenita (DC) is a clinically and genetically heterogeneous multisystem bone marrow failure disorder of telomere maintenance, which may present with dermatological features. The main cause of mortality is bone marrow failure, often developing in the second decade of life, although pulmonary disease and malignancies such as squamous cell carcinomas (SCCs) may also prove fatal. We report the case of a 28‐year‐old man with X‐linked DC and confirmed DKC1 gene mutation. In addition to the classic triad of nail dystrophy, hyperpigmentation and oral leucoplakia, the patient had actinic keratosis (AK) and photodamaged skin, hitherto under‐recognized features of this condition. Awareness of the clinical presentation of DC is important, as accurate clinical and molecular diagnosis affords patients and their families genetic counselling, cancer prevention and screening measures, and planning for complications such as bone marrow failure.     

Porokeratosis of Mibelli following bone marrow transplantation

BACKGROUND: Porokeratosis is a rare disorder of keratinization with both autosomal dominant and acquired forms. Immunosuppression has been associated with the development of porokeratosis in numerous case reports and series. To our knowledge, however, only five cases of porokeratosis have been reported following bone marrow transplantation. RESULTS: We report five cases of porokeratosis of Mibelli following bone marrow transplantation. The diagnosis of porokeratosis was made between 1 and 13 years post-transplantation. The underlying malignancy in four of the five cases was leukemia, while the fifth patient had non-Hodgkin's lymphoma. Porokeratosis developed during remission in the four leukemia patients, whereas, in the fifth patient, it occurred during a relapse of lymphoma. CONCLUSIONS: Porokeratosis may develop following bone marrow transplantation. Our five cases double the number reported in the medical literature, and the incidence of porokeratosis following bone marrow transplantation may be significantly higher than previously recognized. As cutaneous carcinomas have been reported in association with porokeratosis, careful surveillance for porokeratosis in bone marrow transplant recipients is warranted.     

Linear IgA dermatosis in an immunosuppressed patient after allogenic bone marrow transplantation

Linear IgA dermatosis (LAD) is a well-recognized acquired subepidermal bullous autoimmune disease. LAD is characterized by clinical, histopathological and immunopathological findings. We report the case of a 38-year-old man who suffered from a chronic myeloic leukaemia. Although he received immunosuppressive therapy he developed LAD after an allogenic bone marrow transplantation. After diagnosis of LAD was established we started a successful systemic therapy with dapsone, while continuing the preliminary medication. Here we report for the first time on a possible relationship between LAD and bone marrow transplantation in an immunosuppressed patient.