Table 2 Gastrointestinal and associated clinical features of the patients with PIDs and refractory diarrhoea.
Genetic mutation | Patient 1 XIAP Int5(+1)G > A | Patient 2 STAT1 T385M | Patient 3 FOXP3 M370L | Patient 4 STAT3 Int10(−2)A > G | Patient 5 STAT3 G469R |
|---|---|---|---|---|---|
Gastrointestinal manifestations (“+” means positive findings; “-” means negative findings) | |||||
Gender/Onset/Present age | M/10 M/2Y8M (died) | M/1 M/13Y2M | M/NB/4 M (died) | M/5Y/14Y6M | M/15Y2M/19Y3M |
Frequency at worst per day | 16 | 11 | 12 | 7 | 8 |
Bloody-stain | + | + | + | + | + |
Protein-losing enteropathy | − | − | − | − | − |
Failure to thrive | + | + | + | − | − |
Peri-anal abscess | + | + | + | − | + |
Fistula | − | − | − | + | − |
Endoscopic pathology* | |||||
Oesophagus | No definite lesion | Isolated tiny erosions | No definite lesion | No definite lesion | Erythematous mucosa |
Stomach and duodenum | No definite lesion | Scattered erosions at antrum | No definite lesion | No definite lesion | Erythematous mucosa with some erosions at stomach. Ulcer with granulation at duodenal bulb |
Jejunum and ileum | Multiple segments of wall thickening and skipped lesion | No definite lesion | No definite lesion | Perforation and inflammation | Mild inflammatory process at proximal jejunum |
Colon | Cobblestone mucosal pattern and multiple pseudo-polyp-like lesions with aphthous ulceration. Much whitish to yellowish exudates coating on oedematous mucosa. | Some oedematous mucosa | Scattered hyperaemic and oedematous mucosa | Chronic inflammation and perforation | Scattered hyperaemic and oedematous mucosa |
Medication^ for diarrhoea | |||||
Empiric antibiotics, IVIG, prophylactics, methylprednisolone, TPN (10 M) | Empiric antibiotics, IVIG, prophylactics, methylprednisolone, stem cell transplantation, TPN (2Y11M) | Empiric antibiotics, IVIG, prophylactics, methylprednisolone, sirolimus, TPN (3 M) | Empiric antibiotics and IVIG, if flare-up, methylprednisolone, TPN (2Y8M) | Empiric antibiotics and IVIG if flare-up, methylprednisolone, TPN (2 M) | |
Associated symptoms | |||||
(Onset age) | Incomplete HLH (4 M) | MRSA pustulosis (1 M) | Jaundice caused by TPN-relayed | Severe pyoderma and colon perforation | Recurrent MRSA cellulites and carbuncles (2Y) |
Norovirus enteritis (10 M) | BCG-induced lymphadenitis (7 M) | cholestasis (1 M) | |||
Refractory anaemia and thrombocytopenia (1Y) | Refractory pneumonia (7 M) Bronchiectasis (10 M) | ||||
Splenectomy (1Y) | Intermittent oral candidiasis | ||||
Sepsis by Klebsiella pneumonia, extended spectrum β lactamase (ESBL) E. coli, and Candida (1Y) Pneumo-peritoneum from the perforated colon (1Y) | Hepato-splenomegaly (4 M) | ||||
Significant laboratory findings | |||||
Hb mg/dL (>10) | 10.2 | 9.8 | 9.6 | 11.1 | 13.2 |
ESR /min (<45) | 45.0 | 56.1 | 47.2 | 58.2 | 5.0 |
Albumin mg/dL (>3.5) | 2.2 | 3.5 | 1.7 | 3.8 | 4.1 |
Liver function | |||||
AST (13–40 U/L) | 340 | 63 | 53 | 44 | 13 |
ALT (<36 U/L) | 257 | 27 | 45 | 25 | 21 |
Immune assessments | |||||
Neutrophil (2100–4520/mm3) | 1040 | 4361 | 4456 | 4095 | 4460 |
Absolute lymphocytes (2000–6500 /mm3) | 2600 | 245 | 3176 | 3549 | 1934 |
CD4 (31–56%) | 34.6 | 34.2 | 44.5 | 31.9 | 38.7 |
CD4CD45RA (12–45%) | 19.3 | 9.1 | 31.4 | 20.1 | 25.7 |
CD8 (12–35%) | 37.2 | 1.5 | 35.4 | 24.3 | 33.2 |
CD4 memory (**) | 15.2 | 24.5 | 12.2 | 11.4 | 17.2 |
CD19 (6–27%) | 20.3 | 31.4 | 15.2 | 26.6 | 12.8 |
CD19 memory (**) | 1.0 | 0.7 | 2.5 | 0.3 | 1.2 |
NK (3–22%) | 6.1 | 5.3 | 3.1 | 5.8 | 9.7 |
IgM (49–156 mg/dL) | 358 | 252 | 63 | 219 | 92 |
IgG (334–1230 mg/dL) | 527 | 1072 | 673 | 1130 | 877 |
IgA (15–113 mg/dL) | 40 | 434 | 39 | 63 | 136 |
IgE (<100 IU/ml) | 254 | 16 | 2920 | 45900 | 4940 |
Lymphocyte proliferation (cpm) | |||||
PHA 2.5 ug/ml (29228–58457) | 284 | 1453 | 45721 | 32156 | 24783 |
PWM 0.1 ug/ml (11395–28487) | 280 | 787 | 21529 | 15786 | 22146 |
Candida 2.5 ug/ml (5351–13328) | 41 | 53 | 10142 | 8514 | 9327 |
BCG 0.002 ug/ml (1740–4352) | 18 | 16 | 2143 | 4023 | 3417 |
Superoxide production (86–99%) | 87.4 | 94.5 | 94.6 | 89.7 | 91.3 |
TNF-α suppression (4.7–21.4%) | 7.5 | 5.0 | 18.1 | 10.9 | 8.4 |
