Age-dependent presentations of short telomere extrahematopoietic disease
| Age group . | Immunodeficiency . | Liver disease . | Lung disease . | |||
|---|---|---|---|---|---|---|
| Symptoms . | Finding . | Symptoms . | Finding . | Symptoms . | Finding . | |
| Infant | Bloody diarrhea Failure to thriveEnterocolitis Sepsis | Intestinal mucosal atrophy Crypt apoptosis↓ CD19+ B cells↓ IgA | Rare | Rare | Absent | Absent |
| Adolescent/young adult* | Opportunistic infections(eg, herpes zoster reactivation, primary CMV with retinitis/encephalitis; P jirovecii pneumonia; Candida esophagitis) | ↓ CD4+ T cells↓ IgM↓ T-cell repertoire | Splenomegaly Portal HTN Clubbing Dyspnea/hypoxemia Variceal bleeding | Nodular regenerative hyperplasiaA-V malformationsHPSPatchy fibrosis | Usually absent† | Usually absent† |
| Adult | SCC of the skinCMV viremia and disease after lung transplant P jirovecii pneumonia | ↓ CD4+ T cells↓ T-cell repertoire↓ T-cell proliferation | Splenomegaly Portal HTN Clubbing Dyspnea/hypoxemia Atrophic nodular liver Variceal bleeding | Nodular regenerative hyperplasia HPS Overt fibrosis/cirrhosis | Dyspnea/cough Basilar crackles Restrictive PFT findings | IPF-emphysema‡ Other interstitial lung disease |
| Age group . | Immunodeficiency . | Liver disease . | Lung disease . | |||
|---|---|---|---|---|---|---|
| Symptoms . | Finding . | Symptoms . | Finding . | Symptoms . | Finding . | |
| Infant | Bloody diarrhea Failure to thriveEnterocolitis Sepsis | Intestinal mucosal atrophy Crypt apoptosis↓ CD19+ B cells↓ IgA | Rare | Rare | Absent | Absent |
| Adolescent/young adult* | Opportunistic infections(eg, herpes zoster reactivation, primary CMV with retinitis/encephalitis; P jirovecii pneumonia; Candida esophagitis) | ↓ CD4+ T cells↓ IgM↓ T-cell repertoire | Splenomegaly Portal HTN Clubbing Dyspnea/hypoxemia Variceal bleeding | Nodular regenerative hyperplasiaA-V malformationsHPSPatchy fibrosis | Usually absent† | Usually absent† |
| Adult | SCC of the skinCMV viremia and disease after lung transplant P jirovecii pneumonia | ↓ CD4+ T cells↓ T-cell repertoire↓ T-cell proliferation | Splenomegaly Portal HTN Clubbing Dyspnea/hypoxemia Atrophic nodular liver Variceal bleeding | Nodular regenerative hyperplasia HPS Overt fibrosis/cirrhosis | Dyspnea/cough Basilar crackles Restrictive PFT findings | IPF-emphysema‡ Other interstitial lung disease |
A-V, arteriovenous; CMV, cytomegalovirus; HPS, hepatopulmonary syndrome; HTN, hypertension; IgA, immunoglobulin A; IgM, immunoglobulin M; PFT, pulmonary function test; SCC, squamous cell cancer.
These extrahematopoietic manifestations can also present in childhood. In this age group, however, hematologic manifestations are the primary feature (see Figure 2).
Pediatric and young adult onset of pulmonary fibrosis has been precipitated historically by the use of ablative regimens in the bone marrow transplant setting, especially those regimens that include busulfan.
This nomenclature reflects the unique spectrum of lung disease phenotypes seen in the short telomere syndromes in which pulmonary fibrosis can occur alone (most commonly) or in combination with emphysema, particularly in female smokers.