Re: GSH causing pain in 2yo? - candidate for SJS or TENS?

[Guest guest]

IMO, a child's adverse reactions should be taken very seriously!!! For

instance, in response to biopsy-confirmed ileal lymphoid hyperplasia

(often accompanied by lab-tests showing impaired nutritional status) the

drug sulfasalazine may be prescribed. Yet that drug has known adverse

reactions, the worst of which include s- Syndrome (SJS) and

Toxic Epidermal Necrolysis Syndrome (TENS). I'm consulting for a child

who has had strong reactions against DMSA, garlic, and sulfasalazine. My

worry as a researcher is that, for whatever reasons, the child's immune

system may be hyperreacting against sulfur-related molecules and that

SJS or TENS may develop if the offending substances continue to be

included. Hereinbelow are comments and a search sent this morning.

SIMEON THOMAS wrote:

>Hi, we've been using GSH on our son for about 3 weeks. He has 1/2ml of cream in

the morning and 5 days ago we just started 1/2ml of cream in the evening. He is

2 1/2 and weighs 25 lbs.

>

>Ever since we started the evening dose, he wakes up every night screaming and

writhing in pain. He's inconsolable and cries for about 1 to 1 1/2 hours every

night and just twists and turns in the bed while screaming in pain. Are we

giving him too much GSH? This was the dose his DAN doctor recommended. We didn't

see any problems with just the morning dose, although he seems to have lost his

appetite.

>

>We add TTFD on Monday, so I'm really worried about overdosing or doing anything

that will cause our son damage.

>

>Has anyone else had this problem?

>

>Thank you so much!

>

>

* * * * * * *

I am concerned that a child who consistently has a strong reaction

against DMSA, garlic, and sulfasalazine may be at increased risk for

s Syndrome or even Toxic Epidermal Necrolysis Syndrome if

exposure is repeated. Perhaps SJS or TENS is a long-shot for such a

child, but it the child were to develop SJS or TENS from such an

exposure, the parents would rapidly become extremely unhappy. These

syndromes are hugely severe!!!

The search

(sulfasalazine OR sulphasalazine) AND ((stevens AND johnson AND

syndrome) OR (Toxic AND Epidermal AND Necrolysis))

generated 13 citations, all hereinbelow.

SJS and TENS are severe autoimmune reactions, usually against

pharmaceutical medications. Factors within the individual person seem to

be the determinant of why a medication relatively benign for most

individuals produces horrendously severe reactions in a very small

minority.

Today the search

((stevens[ti] AND johnson[ti] AND syndrome) OR (Toxic[ti] AND

Epidermal[ti] AND Necrolysis[ti])) BUTNOT (sulfasalazine OR sulphasalazine)

generated 1600+ citations. The list conveys the wide variety of

pharmaceuticals linked with SJS and TENS. The 1600+ citations are not

presented hereinbelow.

1: Ann Pharmacother. 2003 Sep;37(9):1241-3.

Photo-induced s- syndrome due to sulfasalazine therapy.

Borras-Blasco J, Navarro-Ruiz A, Matarredona J, Devesa P, Montesinos-Ros A,

-Delgado M.

Pharmacy Service, Hospital General Universitario de Elche, Elche, Alicante,

Spain. jborrasb@...

OBJECTIVE: To report a case of photo-induced s- Syndrome (SJS) due

to sulfasalazine therapy. CASE SUMMARY: Photo-induced SJS associated with

sulfasalazine therapy occurred in a 34-year-old white man diagnosed as having

seronegative symmetrical polyarthritis with no predisposing factors. According

to his medical record, the patient had received methotrexate, levofolinate

calcium, deflazacort, and diclofenac sodium as needed. Two months prior to

admission, methotrexate and diclofenac sodium were suspended and treatment with

sulfasalazine was started. The patient presented to our emergency department

because of severe erythema confined to sun-exposed areas; annular lesions on the

extremities and the mucosa were affected. Nikolsky's sign was present. A skin

biopsy was compatible with SJS, and the clinical diagnosis was SJS induced by

sulfasalazine. Administration of sulfasalazine was suspended, which resulted in

an improvement in the skin lesions and general state of health. The patient was

discharged without further symptoms. DISCUSSION: The observed reaction to

sulfasalazine was considered phototoxic, as lesions appeared like a burn rash

reaction in sun-exposed areas when sulfasalazine treatment was started and the

reaction progressed to SJS. It seems that there was a correlation between the

time course of the reaction and the administration of sulfasalazine. An

objective causality assessment revealed that the adverse effect was possible.

CONCLUSIONS: To our knowledge, this is the first report of photo-induced SJS due

to sulfasalazine therapy. Clinicians should be aware of this infrequent but

severe reaction. If clinical evaluation leads to the suspicion of SJS,

sulfasalazine should be discontinued immediately.

Publication Types:

Case Reports

PMID: 12921507 [PubMed - indexed for MEDLINE]

2: Rev Pneumol Clin. 2001 Sep;57(4):297-301.

[Fatal toxic respiratory epitheliolysis. Subacute tracheo-bronchial desquamation

in s- syndrome]

[Article in French]

L, Hazouard E, Michalak-Provost S, Maurage C, Machet L.

Service de Dermatologie, CHU Trousseau, Chambray les Tours, France.

Acute bronchial mucosal sloughing related to Toxic Epidermal Necrolysis (Lyell

syndrome) is widely reported in literature. On the contrary severe respiratory

involvement is rare in post-infectious or toxic Epitheliolysis (s-

syndrome). There is no well-known predictive sign of bronchial epithelium

involvement. An 18-year-old patient was admitted for s- syndrome

related to sulfasalazine (salazosulfapyridine). There were no respiratory signs.

An acute respiratory failure occurred 36 hours after from admission due to an

obstructive and desquamative necrosis of the tracheobronchial epithelium. We

purpose that a fiberoptic laryngoscopy should be performed even in non-dyspneic

patients suffering from s- syndrome if hypersecretion is present.

Fiberoptic bronchoscopy can be helpful in these cases.

Publication Types:

Case Reports

PMID: 11593156 [PubMed - indexed for MEDLINE]

3: Arthritis Rheum. 1995 Apr;38(4):573.

Toxic epidermal necrolysis after sulfasalazine treatment of mild psoriatic

arthritis: warning on the use of sulfasalazine for a new indication.

Jullien D, Wolkenstein P, Roupie E, Roujeau JC, Revuz J.

Hopital Henri Mondor, University of Paris XI, Creteil, France.

Publication Types:

Case Reports

PMID: 7718014 [PubMed - indexed for MEDLINE]

4: Am J Gastroenterol. 1993 Mar;88(3):460-1, 462.

Comment on:

Am J Gastroenterol. 1992 Aug;87(8):1029-32.

Desensitization to sulfasalazine.

Hessemer CA, Schinagl EF.

Publication Types:

Comment

Letter

PMID: 8094941 [PubMed - indexed for MEDLINE]

5: Acta Ophthalmol (Copenh). 1992 Aug;70(4):534-42.

Pseudomembranous and membranous conjunctivitis. Immunohistochemical features.

Kivela T, Tervo K, Ravila E, Tarkkanen A, Virtanen I, Tervo T.

Department of Ophthalmology, Helsinki University Central Hospital, Finland.

A 63-year-old man, who had for one month been on sulfasalazine therapy,

developed general malaise, high fever, severe stomatitis, and bilateral

necrotizing pseudomembranous conjunctivitis with corneal erosion, identical to

that seen in the s- syndrome. Topical therapy with antibiotics and

aprotinin rapidly healed the corneal surfaces, while densely adherent true

membranes developed on the conjunctiva, and were removed surgically several

times during the next week. After the acute stage, subtle subepithelial

conjunctival scarring, superficial punctate keratitis, dry eye syndrome and

fluctuating irregular corneal astigmatism became evident, but good visual

acuity, lid function and ocular motility were retained. Histopathologic study of

conjunctival membranes from two cases of membranous conjunctivitis revealed

polymorphonuclear leukocytes within a matrix composed of fibrin, tenascin and

fibronectin. In older membranes, histiocytes were additionally found. Surgical

debridement of such membranes removes a substratum of inflammatory debris that

is likely to promote secondary infection, fibrosis and symblepharon formation,

and may decrease rather than increase subsequent scarring of the necrotized

conjunctiva.

Publication Types:

Case Reports

PMID: 1384271 [PubMed - indexed for MEDLINE]

6: Am J Gastroenterol. 1992 Aug;87(8):1029-32.

Comment in:

Am J Gastroenterol. 1993 Mar;88(3):460-1, 462.

Sulfasalazine desensitization in children and adolescents with chronic

inflammatory bowel disease.

Tolia V.

Division of Pediatric Gastroenterology, Children's Hospital of Michigan, Wayne

State University, Detroit.

Sulfasalazine is an important therapeutic agent in the management of chronic

inflammatory bowel disease (CIBD). Unfortunately, adverse reactions to this drug

have been reported in 5-55% of treated patients. These include dose-related side

effects like nausea, malaise, and headache or hypersensitivity reactions such as

rash, fever, hives, arthralgia, hepatitis, etc. Studies in adults with

successful reintroduction of sulfasalazine after a desensitization program have

been reported; however, with regard to children, no such data are available.

Fourteen children and adolescents (5-16 yr old) diagnosed to have CIBD

manifested hypersensitivity to sulfasalazine within 2 months of onset of

treatment. All had pancolitis--secondary to Crohn's disease (CD) in four and to

ulcerative colitis (UC) in 10. All of them were on steroids. Sulfasalazine was

discontinued in all after symptoms of hypersensitivity developed. Three patients

with severe reaction were diagnosed prior to desensitization experience.

Desensitization, beginning with 5-50 mg of sulfasalazine/day, was attempted in

the other 11 children. The dose was gradually increased by 5-50 mg increments

every 3 days. Desensitization was successful in only five children, who were

ultimately able to tolerate 1.5-3.0 g of sulfasalazine daily again. In the rest

(six of 11 patients), oral 5-ASA (Asacol) was administered, and three could not

tolerate it. One of these three with intolerance to Asacol required colectomy.

One did not tolerate Asacol or Dipentum. Our findings suggest that sulfasalazine

desensitization should be attempted in all patients developing hypersensitivity

reactions before trying alternative therapy.

PMID: 1353658 [PubMed - indexed for MEDLINE]

7: Br Med J (Clin Res Ed). 1985 Feb 9;290(6466):471-2.

Fatal multisystemic toxicity associated with prophylaxis with pyrimethamine and

sulfadoxine.

Curley RK, Macfarlane AW.

Publication Types:

Case Reports

Letter

PMID: 2857586 [PubMed - indexed for MEDLINE]

8: Ann Intern Med. 1984 Apr;100(4):512-4.

Desensitization for sulfasalazine skin rash.

Purdy BH, Philips DM, Summers RW.

Thirteen patients with inflammatory bowel disease and a documented allergy to

sulfasalazine, manifested by skin rash with or without fever, were enrolled in a

sulfasalazine-desensitization protocol. Twelve patients were successfully

desensitized by using two concentrations of a liquid suspension of

sulfasalazine. Four of thirteen patients developed a rash during the protocol.

Although one patient refused further attempts at desensitization, the remainder

completed the regimen successfully, despite recurrence of the rash on two

occasions in one patient. No predilection to either fast or slow acetylator

phenotype was found. This simple and convenient tolerance induction regimen may

be used safely to desensitize most patients with sulfasalazine allergy

manifested by skin rash with or without fever, despite recurrence of the rash

during tolerance induction. Patients with serious reactions to sulfasalazine,

such as agranulocytosis, toxic epidermal necrolysis, or fibrosing alveolitis,

are not candidates for desensitization.

PMID: 6142671 [PubMed - indexed for MEDLINE]

9: Lancet. 1981 Jul 18;2(8238):151-2.

Drug-dependent binding of circulating antibodies in drug-induced toxic epidermal

necrolysis.

Hensen EJ, Claas FH, Vermeer BJ.

Publication Types:

Case Reports

Letter

PMID: 6113511 [PubMed - indexed for MEDLINE]

10: Tijdschr Ziekenverpl. 1981 Jun 23;34(13):563-7.

[Pathogenesis and treatment of toxic epidermal necrolysis]

[Article in Dutch]

Hensen E.

Publication Types:

Case Reports

PMID: 6115482 [PubMed - indexed for MEDLINE]

11: J R Soc Med. 1980 Aug;73(8):587-8.

Toxic epidermal necrolysis, agranulocytosis and erythroid hypoplasia associated

with sulphasalazine.

Maddocks JL, Slater DN.

Publication Types:

Case Reports

PMID: 6112274 [PubMed - indexed for MEDLINE]

12: Orv Hetil. 1976 Apr 18;117(16):971-3.

[Lyell's syndrome caused by Salazopyrine]

[Article in Hungarian]

Varkonyi V, Torok I, Marta D, Makovitzky J.

PMID: 5694 [PubMed - indexed for MEDLINE]

13: Scand J Infect Dis. 1969;1(3):209-16.

Toxic epidermal necrolysis (Leyell's syndrome). A report on four cases with

three deaths.

Strom J.

PMID: 4398608 [PubMed - indexed for MEDLINE]

[Guest guest]

and Dr. McCandless,

Thank you so much for answering my question. We plan on starting B-12

injections at our next DAN visit (May 30) so we'll probably put the

GSH on hold until after the salts. It figures that my son would be in

the 20% that can't handle GSH.

, your email got me thinking - does GSH contain sulfur? I'm

really naive about all of this, but my son has a similar reaction to

epsom salt baths. There's no pain, but he becomes a live wire and is

unable to sleep after an epsom salt bath. He gets so hyper with even

1/4 cup and stays up all night tossing and turning. I don't know if

there's a connection or not.

The info you sent looks really interesting. Thank you so much for

sending it.

[Guest guest]

> , your email got me thinking - does GSH contain sulfur? I'm

> really naive about all of this, but my son has a similar reaction

to

> epsom salt baths. There's no pain, but he becomes a live wire and

is

> unable to sleep after an epsom salt bath

HUM... My 2 year old son Slater also went nuts after our one and

only epson salt bath.. he was hyper in the tub and for hours

afterwards-much worse than how he was when I put him in the bath. I

guess I need to learn more about this too. He is showing more signs

of aggression but not sure if it is body awareness/sensory issues,

being a typical 2 year old or something else. Another puzzle to

figure out..I read Dr. McCandless' response to someone about

aggressiveness and Glutathione yesterday and wondered about our

situation.

[Guest guest]

Hi . Thanks so much.. I always apprecaite your input so much. I

used about 1/8 cup probably.. I had heard 1/4 but was skeptical

about doing that the first time. This is all so new to me but

several things in your post seem to click with Slater's history. I

will say that we were the perfect example of it not affecting NT

people.. I have " virtual twins " -the same age and had both of them

in the tub. My NT daughter had no reaction at all. But Slater went

off the wall and it took myself and my helper literally to restrain

him at times for about 2 hours. It was one of two times this sort of

thing has happened (other one was one time infraction with casin). I

am seeing minor aggression issues develop I'm afraid and have

wondered about phenols and also read with interest Dr. McCandless'

post on GSH yesterday to another parent. I wish I understood all of

this! And I DO so apprecaite anyone's insight into it. Wish I had

the background to know how to piece it all together.

I know GSH is WONDERFUL for our kids and we use it BID but does it

contain sulfur? I think someone asked that already but I don't

recall seeing an answer though I could have missed it I'm sure. Just

wondering...

Thanks again. I'm going to study your post again and see what else I

might connect.

Blessings,

> ,

>

> How much epsom salts did you use in that first bath? The average

man or

> woman on the street will not have a bad reaction to epsom salts,

so it

> means something unusual is happening. I'm going to repost below