Table 2.
Clinical manifestations in CANDLE/PRAAS and SAVI
| Organ system | Inflammatory manifestations | PRAAS/ CANDLEa fraction (%) |
SAVIb fraction (%) |
End organ damage | PRAAS/ CANDLEa fraction (%) |
SAVIb fraction (%) |
|---|---|---|---|---|---|---|
| Systemic inflammation |
Systemic inflammation (elevated acute phase reactants) |
31/32 (96.9) | 14/14 (100) | Growth retardation/failure to thrive |
24/31 (77.4) | 13/13 (100) |
| Fever | 24/24 (100) | 9/13 (69.2) | Delayed puberty | 6/6 (100) | 3/3 (100) | |
| Anemia | 29/32 (90.6) | 9/9 (100) | Bone marrow suppression | 13/20 (65) | 5/10 (50) | |
| Thrombocytosis | 5/23 (21.7) | 6/7 (85.7) | Thrombocytopenia | 10/20 (50) | 0/7 (0) | |
| Hepatomegaly and/or splenomegaly and/or lymphadenopathy |
29/33 (87.9) | 6/6 (100) | Leukopenia | 2/14 (14.3) | 5/10 (50) | |
| Neutropenia | 2/17 (11.8) | 3/7 (42.9) | ||||
| Lymphopenia | 11/17 (64.7) | 4/8 (50) | ||||
| Skin manifestations | Panniculitis, nodular violaceous erythema |
16/16 (100) | Lipodystrophy | 33/33 (100) | None | |
| Annular plaques | 15/16 (93.8) | Eschars | None | 10/10 (100) | ||
| Acral violaceous plaques, nodules | 12/13 (92.3) | Hyperpigmented macules and scarring |
3/3 (100) | |||
| Erythematous/violaceous rash at cheeks, tip of nose, tips of ears |
13/14 (92.9) | |||||
| Painful distal ulcers with purulent discharge or tissue infarcts |
9/9 (100) | |||||
| Oral ulcers, pustules (including generalized), vesicles |
7/7 (100) | |||||
| Violaceous and or swollen eyelids | 23/25 (92) | |||||
| Perioral swelling | 7/11 (63.6) | |||||
| Vascular manifestations |
Livedo reticularis | 7/7 (100) | Peripheral calcinosis | 2/11 (18.2) | ||
| Raynaud phenomenon | 4/4 (100) | Amputation of extremities |
None | 7/9 (77.8) | ||
| Nailfold capillary changes | 3/3 (100) | Nail dystrophy/loss | None | 6/6 (100) | ||
| Telangiectasia | 8/8 (100) | Systemic hypertension | 7/15 (46.7) | 2/7 (28.6) | ||
| Pulmonary hypertension | 3/13 (23.1) | 2/6 (33.3) | ||||
| Nasal septal perforation | None | 7/9 (77.8) | ||||
| Musculoskeletal manifestations |
Episodic or patchy myositis | 13/19 (68.4) | 3/6 (50) | Muscle atrophy | 13/18 (72.2) | 2/2 (100) |
| Synovitis (non-erosive), arthralgia, stiff joints |
23/25 (92) | 6/12 (50) | Joint contractures | 25/32 (78.1) | 3/4 (75) | |
| Finger swelling | 17/20 (85) | Finger deformities, clubbing |
24/25 (96) | |||
| Myositis, or elevated CK/aldolase | 22/30 (73.3) | 2/5 (40) | ||||
| Metabolic manifestations |
Metabolic syndrome | 4/5 (80) | ||||
| Insulin intolerance, diabetes mellitus |
9/22 (40.9) | 1/4 (25) | ||||
| Dyslipidemiac | 23/31 (74.2) | 4/6 (66.7) | ||||
| Prominent abdomen and/or increased intrabdominal fat |
15/20 (75) | 1/3 (33.3) | ||||
| Acanthosis nigricans | 8/20 (40) | |||||
| Hepatic steatosis | 5/10 (50) | 1/3 (33.3) | ||||
| CNS manifestations | Mild lymphocytic meningitis | 4/16 (25) | Basal ganglia calcifications |
20/29 (69) | 3/7 (42.9) | |
| Headache | 12/13 (92.3) | 3/5 (60) | Cognitive dysfunction/ developmental delay, low IQ |
10/28 (35.7) | 2/8 (25) | |
| Seizures | 3/16 (18.8) | |||||
| Cardiac abnormalitiesd | 6/20 (30) | 1/6 (16.7) | ||||
| Other organ manifestations |
Interstitial lung disease/other lung diseasee |
3/19 (15.8) | 12/14 (85.7) | Lung fibrosis/chronic interstitial lung disease |
9/13 (69.2) | |
| Immune dysregulation |
Autoantibodies (variable, transient) |
11/20 (55) | 13/13 (100) | |||
| Recurrent infectionf | 14/19 (73.7) | 7/7 (100) | ||||
| Low complement (C3 or C4) | 1/13 (7.7) | 0/7 (0) | ||||
| Hypergammaglobulinemia | 9/16 (56.3) | 7/7 (100) |
References. PRAAS/CANDLE: 3, 13–23, 4 previously unpublished patients evaluated or reviewed at NIH, and clinical updates from evaluation at NIH on 8 patients. SAVI: 4, 26–29 with clinical updates on 4 patients, 1 previously unpublished patient evaluated at NIH
Other features seen in PRAAS/CANDLE: transaminitis (n = 16), diarrhea (n = 10), conjunctivitis/episcleritis/keratitis (n = 10), hypertrichosis likely in the context of steroid therapy (n = 6), teeth abnormalities/loss of teeth (n = 4), hyperhidrosis (n = 4), epididymitis/testicular swelling (n = 3), pancreatic abnormalities/pancreatitis (n = 3), dysphagia (n = 3), constipation (n = 2), gynecomastia (n = 2), parotitis (n = 2), renal calculi (n = 1), eosinophilic esophagitis (n = 1), bacterial overgrowth syndrome (n = 1), nephrotic syndrome (n = 1), pericarditis (n = 1), keratoconus (n = 1), IgA nephropathy (n = 1), portal hypertension with esophageal varices (n = 1), nodular regenerative hyper plasia of liver (n = 1), antiphospholipid syndrome with venous thrombosis (n = 1), subarachnoid hemorrhage with cerebral edema (n = 1), bowel pneumatosis (n = 1), undetectable IgA (n = 1)
Other features seen in SAVI: sparse/thin hair (n = 3), tubular/asymptomatic proteinuria (n = 2), transaminitis (n = 2), conductive hearing loss (n = 2), ACPA (or anti-citrullinated peptide antibody) positive erosive arthritis (n = 1), lentigines (n = 1), balanitis (n = 1), hoarse voice (n = 1), lymphedema (n = 1), pectus carinatum (n = 1), gynecomastia (n = 1)
Dyslipidemia features include high LDL, low HDL, and/or hypertriglyceridemia in CANDLE. Only low HDL seen in SAVI
PRAAS/CANDLE cardiac abnormalities: right ventricle dilation in setting of pulmonary hypertension (n = 2), mitral valve prolapse (n = 1), arrhythmia, premature ventricular contraction, congestive heart failure (n = 1), atrial fibrillation (n = 1), right ventricular hypertrophy with secondary repolarization abnormality in setting of pulmonary hypertension (n = 1). SAVI cardiac abnormality: right ventricle dilation in setting of pulmonary hypertension (n = 1)
PRAAS/CANDLE lung disease: interstitial lung disease (n = 1), bronchiolitis-obliterans organizing pneumonia (BOOP)-like lung disease (n = 1), interstitial pneumonitis (n = 1). SAVI lung disease: all interstitial lung disease
PRAAS/CANDLE infections: otitis media (OM), sinusitis, upper respiratory infection (URI), urinary tract infection (UTI), flu, mouth infection, bronchiolitis, sepsis following bowel perforation, pneumonia, oral candidiasis, gingivitis, periodontitis, onychomycosis. SAVI infections: URI, UTI, pneumonia, pansinusitis, oral candidiasis/thrush, otitis externa, OM, recurrent skin infections, cellulitis