A 10-year-old girl was referred to the Paediatric Surgery clinic because of recurrent epigastric and left hypochondrial pain every three months, lasting three to five days. The abdominal discomfort was associated with episodes of nausea. The patient had also had occasional nose bleeds.
At birth she had aspiration of meconium but had been otherwise well until the age of 10. Her father had been diagnosed with ulcerative colitis and her father’s sister had coeliac disease. An ultrasound scan of the abdomen showed a mildly enlarged spleen and a right ovarian follicle. Given her family history, she underwent colonoscopy with biopsy which was inconclusive.
At the age of 19, she was seen in the Gastroenterology clinic and had a repeat abdominal ultrasound scan and additional blood tests. Her scan confirmed a large spleen and the blood tests showed an elevated angiotensin converting enzyme (ACE) level (207 U/L). In view of her splenomegaly, she was referred to the Haematology clinic where she was screened for sarcoid, rheumatoid, haematologic and autoimmune diseases. However, further investigations were normal and no diagnosis could be reached. ACE level was again raised at 250 U/l.
She continued to be afflicted by recurrent episodes of abdominal pain. Therefore she was seen again in the Gastroenterology clinic and was further investigated with oesophago-gastroduodenoscopy with biopsy, ultrasound scan of the liver and portal vein, and abdominal magnetic resonance scan. The enlarged spleen was again evident but no other abnormality was found.
During one of her last clinic consultations, she mentioned that she had been on holiday to the Dominican Republic in 2003 and recalled being bitten by an insect. Following this, she had felt ill for several months with episodes of abdominal pain associated with fever, diarrhoea, nose bleeds and some joint swelling.
She was referred to the Infectious Disease clinic where she was tested for pathogens which could have been encountered during her holiday overseas. These included Epstein–Barr virus, Cytomegalovirus, Toxocara, Leishmania and Schistosomiasis. All tests were negative.
At this time she reported some mild joint swelling and discomfort affecting her fingers. A Rheumatology opinion was sought.
What do you think was the diagnosis?
Shonkus, I seem to have restored the old look you liked, but in the process lost our comments on the latest case- the young chap with rash and peri-anal ulcers. Never mind. The comments on all the other threads are intact.
ReplyDelete....its always a pleasure hearing frm u...tnx for the restoration & equally sad abt the loss....it is not proper on my part to seek alteration in ur blog quality nd presentation...but some how or the other this current reversal to the old format is appealing nd heartening....since,thr is a deluge in cases of Fever, Pneumonitis,Acid Peptic Disorders(agrravated by fast),GE,Acute Abdomen...I am returning home v late past midnite yestday....hence couldnot deliberate on the current v interesting case u posted....though I hv jotted down the gist nd finer pts on whch I am wrking now....she had to visit as many as 6 speciality clinics...I am reading Gaucher's Disease now...will let u know tomorrow surely....Tnx....!!
ReplyDeleteNot to worry. Your patients need you and as I have said before, you deliver a very important service, vital for the well being of that community. The blog can wait. Please take your time. Look forward to discussing with you soon.
ReplyDelete.....High ACE & Insect bite @Dominican Republic holds the key...but ACE levels r often high normally under the age of 20yrs...Insect bite, could it be Mosquito bite...?....Isolated splenomegaly :Hematological 25-66%,Hepatic 12-46%, Infective 13-25%,Primary Splenic 2-5%....hv ruled out Hem Anemia,CML,Hairy cell L, Splenic vein Occlusion:Portal HTN,FELTY synd.Tropical Splenomegaly:i.e rptd attacks of Malaria,,Leishmaniasis,Schistosomiasis ,Post necrotic cirrhosis,....Nontropical splenomegaly: Lymphoma,Myeloid Metaplasia,Cyst & Abscess...but can't rule out Collagen vascular disease,Dacie'Synd.Gaucher's disease...also DF is hovering in the mind.....totally clueless abt the Ulcerative colitis & Coeliac disease angle pertaining to family history as colonoscopy biopsy r normal.....ur further clue or lead wud be of help....!!!....tnx for the much needed CME..!!!
ReplyDeleteWell approached, Shonkus. Certainly, this is a somewhat troubling case because the diagnosis was missed over a period of 9 years by various specialties despite obvious clues. Every specialty did tests of their own, but there was a lack of effort to sum things up, look at all her investigations and reach an unifying diagnosis.
ReplyDeleteThere are a number of red herrings in this case, such as the insect bite during the trip to Dominican Republic. I included these as they represent an actual chronology of events. It's how I found the case when i first saw the girl.
There are two important clues to the diagnosis- the enlarged spleen and the persistently raised ACE level.
Raised ACE levels are considered pathognomonic of sarcoidosis, and although the ACE is elevated in 75% of subjects with sarcoid, it is far from specific, and can be raised in other disorders. ACE is really a marker of macrophage activation. Thus it can be raised in histoplasmosis, tuberculosis, silicosis, leprosy and Hodgkin's disease, among other conditions. However, when you put together her splenomegaly and the rather high ACE, the d/d comes down to 3 or 4 conditions- sarcoid, chronic granulomatous disease of childhood, common variable immunodeficiency and Gauchers Disease. Of these sarcoid had been considered several times, and the second and third conditions present with recurrent infections. Further CGD, being X-linked, favours boys and CVID is associated with very low Ig levels. That leaves Gauchers Disease.
I strongly suspected she had type I Gauchers, which is a relatively benign condition, compared with types II & III and can go undiagnosed for many years. I sent off blood for leucocyte glucocerebrosidase and checked her serum chitotriosidase, which, like ACE, is also a marker of macrophage activation. Her glucocerebrosidase levels were very low- around 2% of normal and chitotriosidase levels were extremely high, conclusive of Gauchers.
I referred her to the lysosomal storage disorders unit at Addenbrookes in Cambridge, who have been administering recombinant glucocerebrosidase, and she feels much better. She is managing to pursue her studies at college.
You mentioned the diagnosis twice in your posts, so full marks for considering it in your d/d!
....the lucidity of your enunciation & conclusive remarks have soared my spirits...in tht I hv a reason now to attempt for the best for GOD's wish has to be carried out....for down further south to homeland this community was waiting for me to be their Hitman to deliver the goods...in a way fate wanted me to excel however reluctant or lethargic I was....with a 10 bed Unit under my sole charge & 50 plus OPD daily with all varieties...which beats the Hell out of me at the end of the day...with misdiagnoses & Incomplete diagnoses galore.....the interest on fire now.....in between cases I am solving papers, may be on exams I will set my eyes...it is never too late ....probably its better now for such an attempt, because I hv reasons to believe, tht the mind is more sharp now, powered by experience...wht do you say..?....I feel I am a true "Medical" representative of the Tropical South Asia handling a bulk of pts of Undivided India,right frm Bangladesh,Nepal, Pakistan ,Sri Lanka,Maldives,in addition to South east Asia including Indonesia,Vietnam,Phillipines,Thailand & Malaysia,handling these Expatriate wrk force in remote Maldives Islands....the similar weather conditions,hot humid Tropical,Equatorial & quite similar Demography with its disease portfolio, I am most comfortable with....u were rt, studying nd its application is most enjoyable now....now tht the Economics & its struggle is no longer a priority.....U r valued presence has simply catalyzed the cascade of Gud feelings & thoughts of well being....Tnx...!!
ReplyDeleteI am very pleased that you feel energized by our discussions. If it helps you make a difference to your patients, then that's served the purpose of this blog.
ReplyDelete