Table 2 The journey towards a diagnosis of primary antibody deficiency

1

Doctor

GP

ENT specialist (1st trajectory)

ENT specialist (2nd trajectory)

Pulmonologist

Oncologist

Signs and symptoms

Recurrent upper airway infections

Recurrent upper airway infections

Recurrent upper airway infections

Chronic cough, episodic dyspnea, especially at night

Recurrent upper airway infections, weight loss, frequent hospital admission for respiratory infections, night sweats, splenomegaly

Attribution

n/a

Nasal polyps

n/a

Asthma

Leukemia, non-Hodgkin lymphoma

Action

Referral to ENT specialist

Polypectomy

Prednisone, antibiotics, tympanoplasty

Pulmonary function test, increasing the dose of inhalation corticosteroids, prophylactic antibiotics

Hospital admission, extensive examinations leading to CVID diagnosis

2

Doctor

GP (1st trajectory)

ENT specialist

GP (2nd trajectory)

Gastro-enterologist

Immunologist

Signs and symptoms

Chronic rhinitis, chronic fatigue, hypothyroidism

Chronic rhinitis

Stomach and bowel complaints, chronic fatigue, frequent GP visits

Stomach and bowel complaints, infiltrative enterocyte lesions (Marsh 1)

Attribution

Chronic rhinitis not further specified

Nasal septum deviation

Gastritis not further specified

Irritable bowel syndrome

Action

Referral to ENT specialist

Septoplasty, steroid nasal spray

Antacids, and after persistent symptoms, referral to gastro-enterologist

Gluten-free diet was considered, peppermint oil, referral to immunologist after IgA-deficiency was discovered

3

Doctor

GP (1st trajectory)

Psychologist

GP (2nd trajectory)

Patient

Immunologist

Signs and symptoms

Chronic cough, recurrent otitis, burn-out symptoms

Feeling worn out, burn-out symptoms

Chronic cough, recurrent otitis, burn-out symptoms

Chronic cough, recurrent otitis, burn-out symptoms, ITP, alopecia areata

See under ‘patient’

Attribution

Recurrent bronchitis in combination with psychological factors

The combination of being always ill, working and taking care of a newborn child

n/a

Some kind of auto-immune disease

Immunologic or auto-immune disorder

Action

Antibiotic treatment, bronchodilators, referral to psychologist

Referral back to GP

Advise to the patient to google to find out the cause of complaints

Arranging own referral to immunologist/

rheumatologist

Extensive laboratory investigations after which the CVID diagnosis was made

4

Doctor

GP (1st trajectory)

Pulmonologist

ENT specialist

GP (2nd trajectory)

Pulmonologist

Immunologist

Signs and symptoms

Recurrent rhinitis/ pneumonia/ sinusitis

Recurrent rhinitis/ pneumonia/ sinusitis

Recurrent rhinitis/ pneumonia/ sinusitis

Persistent, recurrent respiratory infections, meningitis

Persistent, recurrent respiratory infections, meningitis

Persistent, recurrent respiratory infections, meningitis, inguinal lymphadenopathy, weight loss

Attribution

n/a

Obstruction of sinus drainage, bacterial pneumonia

Obstruction of sinus drainage

n/a

Bacterial pneumonia

PID

Action

Referral to pulmonologist

Chest X-ray, therapeutic and prophylactic antibiotic treatment, referral to ENT specialist

Endoscopic sinus surgery

Referral to pulmonologist

Chest X-ray, antibiotics, referral to immunologist after IgA-deficiency was discovered

Extensive laboratory investigations after which the CVID diagnosis was made

5

Doctor

GP

Immunologist

Signs and symptoms

Recurrent meningitis, otitis, chronic sinusitis, positive family history

Recurrent meningitis, otitis, chronic sinusitis, positive family history

Attribution

PID

Action

Referral to immunologist

Extensive laboratory investigations after which the XLA diagnosis was made

6

Doctor

GP

Pulmonologist (1st trajectory)

Pulmonologist (2nd trajectory)

Signs and symptoms

Recurrent respiratory infections / sinusitis / pneumonia, bronchial hyperreactivity, fatigue, exercise intolerance

Recurrent respiratory infections / sinusitis / pneumonia, bronchial hyperreactivity, fatigue, exercise intolerance

Streptocococcus pneumoniae pneumonia and persistent Haemophilus influenzae colonization despite antibiotic treatment

Attribution

n/a

Bacterial pneumonia and asthma

Possible CVID

Action

Referral to pulmonologist

Sputum cultures, therapeutic and prophylactic antibiotic treatment

After discovery of low serum immunoglobulins, treatment with intravenous immunoglobulins

7

Doctor

Pediatrician

Signs and symptoms

Recurrent otitis / rhinitis / sinusitis, chronic cough, skin abscess, pneumonia, failure to thrive

Attribution

PID

Action

Extensive laboratory investigations after which the unPAD diagnosis was made

8

Doctor

GP (1st trajectory)

Pulmonologist

ENT specialist

GP (2nd trajectory)

Immunologist

Signs and symptoms

Recurrent otitis/ rhinitis/ sinusitis/ pneumonia

Recurrent otitis/ rhinitis/ sinusitis/ pneumonia

Recurrent otitis/ rhinitis/ sinusitis/ pneumonia

His two sons were diagnosed with CVID by a pediatrician

Recurrent otitis/ rhinitis/ sinusitis/ pneumonia, two sons were diagnosed with CVID by a pediatrician, recurrent varicella zoster and Giardia lamblia infections, warts, anosmia

Attribution

n/a

Bacterial pneumonia

Nasal septum deviation/ polyps

Possible CVID

Possible CVID

Action

Referral to ENT specialist and pulmonologist

Prophylactic and repeated therapeutic antibiotic treatment

Prophylactic and repeated therapeutic antibiotic treatment

Referal to immunologist

Extensive laboratory investigations after which the CVID diagnosis was made

9

Doctor

GP (1st trajectory)

GP (2nd trajectory)

GP (3rd trajectory)

Pulmonologist

ENT specialist

Immunologist

Signs and symptoms

Recurrent otitis/ sinusitis/ skin infections, poor wound healing, chicken pox (2x), mumps

Dyspnea, wheezing, chronic cough

Fatigue, stomach and bowel complaints

Dyspnea, wheezing, chronic cough, recurrent respiratory infections

Recurrent sinusitis and pneumonia despite PnPS and Hib vaccination and antibiotic treatment

Recurrent sinusitis and pneumonia despite PnPS and Hib vaccination and antibiotic treatment

Attribution

Recurrent infections in infancy

Asthma

Graves’ disease

Asthma

Possible PID

Possible PID

Action

None

Inhalation corticosteroids, referral to pulmonologist

Antithyroid medication

Increasing the dose of inhalation corticosteroids, repeatedly oral prednisolone and antibiotic treatment

Functional endoscopic sinus surgery and referral to immunologist

Extensive laboratory investigations after which the unPAD diagnosis was made

10

Doctor

GP (1st trajectory)

GP (2nd trajectory)

GP (3rd trajectory)

GP (4th trajectory)

Internist (1st trajectory)

Internist (2nd trajectory)

Signs and symptoms

Fatigue, aphthous lesions

Erythema nodosum

Erythema nodosum + splenomegaly

Erythema nodosum + splenomegaly, enlarged supraclavicular lymph node

Erythema nodosum + splenomegaly, enlarged supraclavicular lymph node

Erythema nodosum + splenomegaly, enlarged supraclavicular lymph node

Attribution

Iron deficiency anemia

Mosquito bites

Some kind of viral infection

Possible malignancy

Sarcoidosis

Action

Iron supplementation

‘Wait and see’

Blood test showed mild pancytopenia; initially ‘wait and see’

Referral to internist

Exclusion of lymphoma after histological examination of lymph node, chest X-ray, discussion in a multidisciplinary team

After suggestion of a colleague to test for immunoglobulins, the diagnosis of CVID was made

11

Doctor

GP

Pediatrician (1st trajectory)

ENT specialist

Pediatrician (2nd trajectory)

Pulmonologist

Immunologist

Signs and symptoms

Recurrent rhinitis/ otitis/ sinusitis, fatigue, growth retardation, chronic diarrhea

Recurrent rhinitis/ otitis/ sinusitis, fatigue, growth retardation, chronic diarrhea

Recurrent rhinitis/ otitis/ sinusitis, fatigue, growth retardation, chronic diarrhea

Persistent infections despite prophylactic antibiotics and multipe ENT surgeries, extreme fatigue, growth retardation

Persistent infections despite prophylactic antibiotics and multipe ENT surgeries, extreme fatigue, growth retardation

Persistent infections despite prophylactic antibiotics and multipe ENT surgeries, extreme fatigue, growth retardation

Attribution

Possible celiac disease, recurrent infections in infancy

Reactive mucosa, recurrent infections in infancy

Combination of recurrent infections in infancy and psychological factors

Possible CF/PCD

Possible selective IgA-deficiency

Action

Referral to ENT specialist en pediatrician

Referral to dietician, prophylactic antibiotics after low IgA was discovered during screening for celiac disease

Tonsillectomy, adenotomy, tympanoplasty, functional endoscopic sinus surgery

Referal to psychologist en pulmonologist

Analyses for CF and PCD were negative; referral to immunologist

Selective IgA-deficiency confirmed

12

Doctor

Pediatrician

Pulmonologist (1st trajectory)

ENT specialist

Pulmonologist (2nd trajectory)

Signs and symptoms

Recurrent sinusitis/ pharyngitis/ respiratory tract infections, fatigue

Multiple hospital admisions due to asthma (> 40x)

Recurrent sinusitis/ pharyngitis/ respiratory tract infections, fatigue, retropharyngeal abcess

Still frequent asthma exacerbations despite high-dose inhalation corticosteroids

Attribution

(Severe) asthma and multiple allergies

(Severe) asthma and multiple allergies

Reactive mucosa, bacterial infections

(Severe) asthma and multiple allergies

Action

Inhalation corticosteroids, referal to pulmonologist and ENT specialist

Frequently oral prednisolone, increasing the dose of inhalation corticosteroids, repeatedly antibiotics, subcutaneous epinephrine always available

Abscess drainage, tonsillectomy, multiple sinus surgeries

IgG-subclass deficiency discovered after immunological screening

13

Doctor

GP (1st trajectory)

GP (2nd trajectory)

GP (3rd trajectory)

Internist (1st trajectory)

Internist (2nd trajectory)

Pulmonologist

Signs and symptoms

Iron deficiency anemia, recurrent lymphadenopathy and cystitis, fatigue

Recurrent respiratory infections (including proven pneumonia)/ sinusitis/ otitis

Chronic diarrhea, abdominal pain

Chronic diarrhea, abdominal pain

Persistent abdominal pain, vomiting, recurrent respiratory infections

Persistent abdominal pain, vomiting, recurrent respiratory infections

Attribution

Some kind of viral infection

Asthma, bacterial pneumonia

Possible diverticulitis

Possible diverticulitis

n/a

CVID, possible bronchiectasis

Action

Follow-up

Antibiotics, inhalation corticosteroids, oral prednisolone

Referal to internist

Abdominal CT confirmed diverticulitis and kidney stones

Extensive laboratory investigations after which CVID was diagnosed, referal to pulmonologist for screening for bronchiectasis

Thymoma was coincidentally found on chest CT scan, Good syndrome was diagnosed

14

Doctor

GP (1st trajectory)

Gynaecologist

GP (2nd trajectory)

Psychiatrist

Patient

Immunologist

Signs and symptoms

Recurrent sinusitis and pneumonia, odontogenic infections, sepsis

Severe wound infection after cesarean section

Fatigue, exercise intolerance

Fatigue, exercise intolerance

Recurrent sinusitis and pneumonia, odontogenic infections, sepsis, fatigue, exercise intolerance, persistent Helicobacter Pylori and Giardia lamblia infections despite treatment, recurrent cystitis, chronic slightly elevated body temperature

Recurrent sinusitis and pneumonia, odontogenic infections, sepsis, fatigue, exercise intolerance, persistent Helicobacter Pylori and Giardia lamblia infections despite treatment, recurrent cystitis, chronic slightly elevated body temperature

Attribution

Viral and bacterial infections

Bacterial infection

Menopause and psychological factors

Psychological factors

Possible PID

Possible PID

Action

Repeatedly antibiotics

Prophylactic antibiotics during second cesarean section

Referral to psychiatrist

Treatment for stress (not further specified)

Arranging own referral to immunologist

Extensive laboratory investigations after which CVID was diagnosed