Can a decision support system accelerate rare disease diagnosis? Evaluating the potential impact of Ada DX in a retrospective study

Background Rare disease diagnosis is often delayed by years. A primary factor for this delay is a lack of knowledge and awareness regarding rare diseases. Probabilistic diagnostic decision support systems (DDSSs) have the potential to accelerate rare disease diagnosis by suggesting differential diagnoses for physicians based on case input and incorporated medical knowledge. We examine the DDSS prototype Ada DX and assess its potential to provide accurate rare disease suggestions early in the course of rare disease cases. Results Ada DX suggested the correct disease earlier than the time of clinical diagnosis among the top five fit disease suggestions in 53.8% of cases (50 of 93), and as the top fit disease suggestion in 37.6% of cases (35 of 93). The median advantage of correct disease suggestions compared to the time of clinical diagnosis was 3 months or 50% for top five fit and 1 month or 21% for top fit. The correct diagnosis was suggested at the first documented patient visit in 33.3% (top 5 fit), and 16.1% of cases (top fit), respectively. Wilcoxon signed-rank test shows a significant difference between the time to clinical diagnosis and the time to correct disease suggestion for both top five fit and top fit (z-score -6.68, respective -5.71, α=0.05, p-value <0.001). Conclusion Ada DX provided accurate rare disease suggestions in most rare disease cases. In many cases, Ada DX provided correct rare disease suggestions early in the course of the disease, sometimes at the very beginning of a patient journey. The interpretation of these results indicates that Ada DX has the potential to suggest rare diseases to physicians early in the course of a case. Limitations of this study derive from its retrospective and unblinded design, data input by a single user, and the optimization of the knowledge base during the course of the study. Results pertaining to the system’s accuracy should be interpreted cautiously. Whether the use of Ada DX reduces the time to diagnosis in rare diseases in a clinical setting should be validated in prospective studies. Electronic supplementary material The online version of this article (10.1186/s13023-019-1040-6) contains supplementary material, which is available to authorized users.


Diagnosis
Female 63  Female 59 spots on the lower extremity (color: purple time since onset: one day to one week) groin pain purpura lower extremity pain (laterality: bilateral) swelling of the lower leg (laterality: bilateral time since onset: one day to one week) fever (time since onset: one day to one week high grade: no) chills (time since onset: one day to one week)

Diagnosis
Female 60 Henoch-Schonlein Purpura (HSP) spots on the lower extremity (color: purple time since onset: one week to one month) groin pain (time since onset: one week to one month) purpura lower extremity pain (laterality: bilateral time since onset: one week to one month) swelling of the lower leg (

Top Five Fit
Female 27 feeling of heavy legs (time since onset: one month to one year) epistaxis (time since onset: one month to one year) fever (time since onset: one month to one year) malaise (time since onset: one month to one year repeat consult: yes) myalgia (time since onset: one month to one year) hearing deficit (laterality: unilateral time since onset: one month to one year)

Top Fit (<= 1 month early)
Female 27 feeling of heavy legs (time since onset: one month to one year) epistaxis (time since onset: one month to one year) fever (time since onset: one month to one year) malaise (time since onset: one month to one year repeat consult: yes) myalgia (time since onset: one month to one year) hearing deficit (laterality: bilateral time since onset: one month to one year) otalgia lower extremity pain (laterality: bilateral) gait impairment fatigue

Diagnosis
Female 27 Granulomatosis with Polyangiitis (GPA) feeling of heavy legs (time since onset: one month to one year) epistaxis (time since onset: one month to one year) fever (time since onset: one month to one year) malaise (time since onset: one month to one year repeat consult: yes) myalgia (time since onset: one month to one year) hearing deficit (laterality: bilateral time since onset: one month to one year) otalgia lower extremity pain (laterality: bilateral) gait impairment fatigue CRP, elevated cytoplasmic antineutrophil cytoplasmic antibodies present proteinase 3 antibody titer, elevated perinuclear anti-neutrophil cytoplasmic antibodies present

Diagnosis
Female 53 Antisynthetase Syndrome vomiting (time since onset: more than one year) cholesterol level (result: elevated) steatosis hepatis lower back pain (time since onset: more than one year) finger joint pain (time since onset: more than one year) tricolor pattern of discoloration of the fingers and toes (time since onset: more than one year) diarrhea (time since onset: more than one year) groin pain (time since onset: more than one year) swelling, finger joints (time since onset: more than one year) morning stiffness (time since onset: more than one year) shoulder pain (time since onset: more than one year) neck pain (time since onset: more than one year) insomnia rapid pulse ( wrist pain (time since onset: more than one year laterality: unilateral) swelling, wrist (time since onset: more than one year) finger joint pain (time since onset: more than one year laterality: bilateral) swelling, finger joints (time since onset: more than one year) ankle pain (time since onset: more than one year laterality: unilateral) swelling, ankle joint (time since onset: more than one year laterality: unilateral) uric acid level (result: elevated) headache joint space narrowing of the fingers

Diagnosis
Female 45 Gout arthritis immunocompromised status Hx: hypertension wrist pain (time since onset: more than one year laterality: unilateral) swelling, wrist (time since onset: more than one year) ankle pain (time since onset: more than one year laterality: unilateral) swelling, ankle joint (time since onset: more than one year laterality: unilateral) uric acid level (result: elevated) headache (time since onset: one month to one year) joint space narrowing of the fingers lower back pain (time since onset: one month to one year) MCP joint pain (time since onset: one month to one year) swelling, MCP joints (time since onset: one month to one year) diabetes mellitus sensory deficit, hand antinuclear antibody level, elevated elevated rheumatoid factor 69 Visit

Top Five Fit
Male 57 elevated BMI nausea (time since onset: more than one year) rapid pulse (time since onset: more than one year) chest pain (position: unilateral time since onset: more than one year sharp: yes) aural fullness (time since onset: more than one year) hyperhidrosis, generalized (cold perspiration: yes time since onset: more than one year) headache (time since onset: more than one year) vertigo (time since onset: more than one year) upper extremity pain (laterality: unilateral time since onset: more than one year) neck pain (time since onset: more than one year) high blood pressure (time since onset: more than one year) lower back pain (time since onset: more than one year activity: exacerbates nocturnal or early morning: exacerbates) sensory deficit, hand (distribution: bilateral, symmetrical time since onset: more than one year) painful dysesthesia of the upper extremity (distribution: symmetrical time since onset: more than one year) painful dysesthesia of the lower extremity (distribution: symmetrical time since onset: more than one year) paresthesia of the hand (distribution: symmetrical time since onset: more than one year) paresthesia of the lower extremity (distribution: symmetrical time since onset: more than one year) sensory deficit, foot (distribution: bilateral, symmetrical reduced vibration sense: yes impaired proprioception: yes time since onset: more than one year) Premature ventricular contraction ventricular tachycardia aortic valve regurgitation on imaging dyspnea (severity: on exertion time since onset: more than one year) LDL level (