Clinical, immune, and radiological assessments pre-sirolimus and pre-leniolisib treatments
| . | Pre-sirolimus assessment . | Details pre-sirolimus . | Pre-leniolisib assessment . | Details pre-leniolisib . |
|---|---|---|---|---|
| Age | 12 years 6 mo | | 14 years 1 mo | |
| Weight | 29.4 kg | −2.39 SD | 34.8 kg | −2.53 SD |
| Height | 133.1 cm | −2.80 SD | 147.9 cm | −2.04 SD |
| Clinical manifestation | Severe recurrent infections | Encephalitis—HHV-6 Sepsis—S. aureus Recurrent otitis—P. aeruginosa Pneumonia RSV—M. pneumoniae | Recurrent respiratory infections | Upper respiratory infection not requiring hospitalization |
| Alopecia areata | Alopecia areata of the scalp, three patches, partial response to topical and systemic steroids | Alopecia areata | Smaller patches and fluctuating course with topical steroids | |
| Dysimmune hepatitis | Hepatitis with mild cholestasis and normal liver function. Anti-SM antibodies positivity and anti-LKM antibodies negativity. Histology: Rich portal and lobular lymphocytic infiltrate with occasional interface expression with CD3+ as predominant component. | Dysimmune hepatitis | Residual self-limiting sporadic increase in transaminase levels | |
| Splenomegaly | Spleen (US) 16 cm (bipolar diameter) with hypoechoic intraparenchymal areas with a maximum diameter of ∼19 mm | Splenomegaly | Spleen (US) 12 cm (bipolar diameter), heterogeneous echotexture due to the persistence of some hypoechoic areas with ill-defined margins, not clearly vascularized, and containing some hyperechoic components consistent with calcifications Spleen (MRI) 13 cm, with some vaguely hypointense nodular-like areas are observed on T2W | |
| Persistent lymphadenopathies | US (max dimensions) LTC lymph nodes L 21 × 9 mm, R 14 × 6 mm | Fluctuating lymphadenopathies | US (max dimensions) LTC lymph nodes R 15 × 6 mm; L 14 × 5 mm, reduced echogenicity and poor visualization of the hilum Submandibular lymph nodes R 20 × 6 mm; L 15 × 7 mm, regular echotexture Axillary lymph nodes R 15 × 3 mm; L 12 × 6 mm, regular echotexture Supra clavicular lymph nodes L 10 × 4 mm, regular echotexture MRI (max dimensions) LTC lymph nodes 2.3 cm Armpit lymph nodes 1.9 cm | |
| Enteritis | Alternating bowel habits with episodes of diarrhea EGDs: Macroscopically normal findings Colonoscopy: Findings normal except for aptha on the edge of the ileocecal valve Histology: Increased neutrophilic, eosinophilic, lympho-plasmacytic, and granulocytic inflammatory component partially aggressive with plasma cells. Numerous foamy histiocytes in the left colon. Marked increase in duodenal intraepithelial T cells. Complete intestinal metaplasia of the gastric antrum | Pulmonary interstitial disease | CT scan: multiple areas of air trapping with subsegmental distribution in the right lower lobe. Hypoventilation. Bilateral basal fibrotic hypoventilatory streaks Plethysmography: Air trapping with increased airway resistance. TLC: 2.72 L (78%), RV: 1.27 L (146%), RV/TLC: 44 (178%). FEV1/FVC 93% DLCO 4.77 (73%) for VA reduced (2.09, 58%). Kco slightly increased (2.28, 124%) | |
| Thymic hyperplasia | CT (diameter): 5 × 1.7 × 7 cm, cervical extension to the jugular veins, contrast enhancement | |||
| Hematological | Thrombocytopenia Persistent leukopenia Anemia | Worst value recorded PLT count, 124.000/mm3 WBC count, 2,020/mm3 Hb level, 9 g/dl | Thrombocytopenia Fluctuant leukopenia | Worst value recorded PLT count, 114.000/mm3 WBC count, 2,420/mm3 |
| Immune evaluation | Major immunophenotype anomalies: B cells (CD19+) Reduced memory B Slightly expanded transitional B cell Slightly expanded CD21low Senescent CD8 | 15% (124 cell/µl) 1% (39% non-switched) 10% 4.7% n.a. | Major immunophenotype anomalies: B cells (CD19+) Memory B cell Expanded transitional B cell Slightly expanded CD21low Expanded senescent CD8 | 11% (120 cells/ul) 4% (89% non-switched) 20% 4.2% 13% |
| IgG IgM IgA | 934 mg/dl preinfusion in IRT 257 mg/dl 68 mg/dl | IgG IgM IgA | 1,007 mg/dl 66 mg/dl 38 mg/dl | |
| Medications | | Dosage/frequency | | Dosage/frequency |
| SCIG replacement | 15 g/mo | SCIG replacement | 15 g/mo | |
| PEP mask | prescribed but not performed | PEP mask | prescribed but not performed | |
| TMP-SMX | 160 mg/800 mg | TMP-SMX | 160 mg/800 mg | |
| Folic acid | one tablet three times per wk | Folic acid | 1 tablet three times per wk | |
| Phytomenadione | 5 mg/day twice per wk | Phytomenadione | 5 mg/day twice per wk | |
| Cholecalciferol 25,000 IU | One vial every 3 wk | Cholecalciferol 25,000 UI | 1 vial every 3 wk | |
| | | Sirolimus | 3.5 mg/day | |
| | | Testosterone | 25 mg/mo intramuscular |
| . | Pre-sirolimus assessment . | Details pre-sirolimus . | Pre-leniolisib assessment . | Details pre-leniolisib . |
|---|---|---|---|---|
| Age | 12 years 6 mo | | 14 years 1 mo | |
| Weight | 29.4 kg | −2.39 SD | 34.8 kg | −2.53 SD |
| Height | 133.1 cm | −2.80 SD | 147.9 cm | −2.04 SD |
| Clinical manifestation | Severe recurrent infections | Encephalitis—HHV-6 Sepsis—S. aureus Recurrent otitis—P. aeruginosa Pneumonia RSV—M. pneumoniae | Recurrent respiratory infections | Upper respiratory infection not requiring hospitalization |
| Alopecia areata | Alopecia areata of the scalp, three patches, partial response to topical and systemic steroids | Alopecia areata | Smaller patches and fluctuating course with topical steroids | |
| Dysimmune hepatitis | Hepatitis with mild cholestasis and normal liver function. Anti-SM antibodies positivity and anti-LKM antibodies negativity. Histology: Rich portal and lobular lymphocytic infiltrate with occasional interface expression with CD3+ as predominant component. | Dysimmune hepatitis | Residual self-limiting sporadic increase in transaminase levels | |
| Splenomegaly | Spleen (US) 16 cm (bipolar diameter) with hypoechoic intraparenchymal areas with a maximum diameter of ∼19 mm | Splenomegaly | Spleen (US) 12 cm (bipolar diameter), heterogeneous echotexture due to the persistence of some hypoechoic areas with ill-defined margins, not clearly vascularized, and containing some hyperechoic components consistent with calcifications Spleen (MRI) 13 cm, with some vaguely hypointense nodular-like areas are observed on T2W | |
| Persistent lymphadenopathies | US (max dimensions) LTC lymph nodes L 21 × 9 mm, R 14 × 6 mm | Fluctuating lymphadenopathies | US (max dimensions) LTC lymph nodes R 15 × 6 mm; L 14 × 5 mm, reduced echogenicity and poor visualization of the hilum Submandibular lymph nodes R 20 × 6 mm; L 15 × 7 mm, regular echotexture Axillary lymph nodes R 15 × 3 mm; L 12 × 6 mm, regular echotexture Supra clavicular lymph nodes L 10 × 4 mm, regular echotexture MRI (max dimensions) LTC lymph nodes 2.3 cm Armpit lymph nodes 1.9 cm | |
| Enteritis | Alternating bowel habits with episodes of diarrhea EGDs: Macroscopically normal findings Colonoscopy: Findings normal except for aptha on the edge of the ileocecal valve Histology: Increased neutrophilic, eosinophilic, lympho-plasmacytic, and granulocytic inflammatory component partially aggressive with plasma cells. Numerous foamy histiocytes in the left colon. Marked increase in duodenal intraepithelial T cells. Complete intestinal metaplasia of the gastric antrum | Pulmonary interstitial disease | CT scan: multiple areas of air trapping with subsegmental distribution in the right lower lobe. Hypoventilation. Bilateral basal fibrotic hypoventilatory streaks Plethysmography: Air trapping with increased airway resistance. TLC: 2.72 L (78%), RV: 1.27 L (146%), RV/TLC: 44 (178%). FEV1/FVC 93% DLCO 4.77 (73%) for VA reduced (2.09, 58%). Kco slightly increased (2.28, 124%) | |
| Thymic hyperplasia | CT (diameter): 5 × 1.7 × 7 cm, cervical extension to the jugular veins, contrast enhancement | |||
| Hematological | Thrombocytopenia Persistent leukopenia Anemia | Worst value recorded PLT count, 124.000/mm3 WBC count, 2,020/mm3 Hb level, 9 g/dl | Thrombocytopenia Fluctuant leukopenia | Worst value recorded PLT count, 114.000/mm3 WBC count, 2,420/mm3 |
| Immune evaluation | Major immunophenotype anomalies: B cells (CD19+) Reduced memory B Slightly expanded transitional B cell Slightly expanded CD21low Senescent CD8 | 15% (124 cell/µl) 1% (39% non-switched) 10% 4.7% n.a. | Major immunophenotype anomalies: B cells (CD19+) Memory B cell Expanded transitional B cell Slightly expanded CD21low Expanded senescent CD8 | 11% (120 cells/ul) 4% (89% non-switched) 20% 4.2% 13% |
| IgG IgM IgA | 934 mg/dl preinfusion in IRT 257 mg/dl 68 mg/dl | IgG IgM IgA | 1,007 mg/dl 66 mg/dl 38 mg/dl | |
| Medications | | Dosage/frequency | | Dosage/frequency |
| SCIG replacement | 15 g/mo | SCIG replacement | 15 g/mo | |
| PEP mask | prescribed but not performed | PEP mask | prescribed but not performed | |
| TMP-SMX | 160 mg/800 mg | TMP-SMX | 160 mg/800 mg | |
| Folic acid | one tablet three times per wk | Folic acid | 1 tablet three times per wk | |
| Phytomenadione | 5 mg/day twice per wk | Phytomenadione | 5 mg/day twice per wk | |
| Cholecalciferol 25,000 IU | One vial every 3 wk | Cholecalciferol 25,000 UI | 1 vial every 3 wk | |
| | | Sirolimus | 3.5 mg/day | |
| | | Testosterone | 25 mg/mo intramuscular |
Ab, antibody; DLCO, diffusing capacity of the lungs for carbon monoxide; EGDs, esophagogastroduodenoscopies; Hb, hemoglobin; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; HHV6, human herpesvirus 6; IRT, immunoglobulin replacement therapy; Kco, carbon monoxide transfer coefficient; LKM, liver kidney microsome; L, left; LTC, laterocervical; PEP, positive expiratory pressure; PLT, platelet; R, right; RSV, respiratory syncytial virus; RV, residual volume; SCIG, subcutaneous immunoglobulin; SM, smooth muscle; TLC, total lung capacity; TMP-SMX, trimethoprim-sulfamethoxazole; UI, international units; US, ultrasound; VA, alveolar volume; WBC, white blood cell.