[Previous Months][Date Index][Thread Index][Join - Register][Login]
  [Message Prev][Message Next][Thread Prev][Thread Next]

RE: [IPm] Pruritis with Humalog and Novolog

Dear George McKnight:

Pruritis and urticaria certainly can occur with m-cresol.  Both Humalog and
Novolog contain m-cresol.  I was unable to find published information about
m-cresol in the Humulins, but I believe that they contain it as well (A call
to Lilly would clarify this.).  The fact that the pruritis did not recur for
six months after switching to Novolog, which definitely does contain
m-cresol, is enough to argue against m-cresol as the cause, however, since
it should not take so long for a reaction to occur during a rechallenge.

Vials of Humalog and the Humulins have latex-containing stoppers, Lantus
vials do not, and I am not sure about Novolog or the Novolins.  However, the
apparent lack of reactions with Humulin-L argues against latex allergy as
the culprit.

Some plasticizers can cause hypersensitivity reactions.

A trial of different reservoirs and lines and of a needle (instead of a
plastic catheter) would be reasonable.  You could also infuse
non-bacteriostatic water by the insulin pump.  You could test minute
injections of the suspect insulins.  Concern about a systemic reaction may
make it prudent to do the trials under controlled circumstances, with
epinephrine, injectable antihistamines and glucocorticoids, and possibly
intubation equipment available.  Insulin-binding antibodies could be
checked, and you might want to specify that a series of assays be performed
competitively with lispro, aspart, and Humulin-L insulin-zinc suspension;
much greater displacement of labeled regular insulin by lispro and aspart
insulin than by insulin-zinc suspension would support, but not prove, the
possibility that this represents an antibody response specific to these
insulin analogues.  I am not sure if RAST testing is available for the
different types of insulin or for m-cresol.  Skin testing does not sound
promising, since the reaction is systemic, rather than local.

Adding a small amount of a glucocorticoids is supposed to help with local
reactions, but a systemic reaction would require such large doses as to
cause their own systemic complications.  If the reaction is due to something
specific to the infusion apparatus, either an appropriate component change
or intensified conventional insulin therapy could solve the problem.  If the
reaction is due to m-cresol, perhaps Lilly or Novo-Nordisc could specially
provide the insulin without a preservative (Using insulin without a
preservative in a pump would necessitate DAILY changes of the insulin,
cartridge, line, and possibly the catheter.  Since the insulin would not be
FDA-approved for marketing, the pharmaceutical company would not be able to
charge for it and might even be required to submit an Investigational New
Drug application.  I suspect that they would want very good reasons before
going through all of the trouble.).  If it turns out that the systemic
reaction is specific to Novolog and Humalog insulins, I think that you have
four choices:  (1) Intensified conventional insulin therapy, preferably with
basal insulinization using glargine and boluses using regular insulin (an
admittedly sorry excuse for fast-acting insulin!); (2) Continuous
subcutaneous insulin therapy with buffered regular insulin (in my opinion,
not worth the complexity of a pump); (3) Antihistamine therapy, possibly
with both an H1- and an H2-blocker (assuming that the risk of anaphylaxis or
angioedema is very low and that the patient and his family have constant
access to an anaphylaxis kit); (4) Rapid desensitization therapy with very
frequent injections of the offending insulin (at injection intervals that I
believe are measured in minutes, increasing in tiny increments from almost
homeopathic doses).

Most likely, however, the apparent association of the pruritis with insulin
pump therapy or insulin analogues is coincidental.  While it is possible to
have a true allergic response in the absence of urticaria, I am skeptical in
this case.  It seems odd that the pruritis would resolve with Humulin-L.
Lente insulins are in a three-dimensionally altered (precipitated) form with
zinc, which is itself an effective adjuvant (immune response enhancer);
unless the exposure to Humulin-L has been brief, it is not obvious why
immune responses would occur with the analogues, but not with Humulin-L.
Although sugar moieties on the surfaces of proteins are at least as
important as the amino acid sequences in determining an immune response,
none of the recombinant insulin products are glycosylated (unlike animal
insulins), so that could not explain an apparent difference in responses to
these insulins.

There are many causes of pruritis, not all of which are allergic.  Dry skin
commonly results from over bathing and less commonly from hypothyroidism or
hypogonadism (both being conditions to which type 1 diabetics are
predisposed).  Of course, one must consider all of the usual causes of
contact sensitivity, including occupational and recreational chemical
exposures and irritating plants.  Other drug, "food" dye, and systemic
environmental chemical exposures are also possibilities.  It is likely that
a lot of supposed adult food allergies are misdiagnoses, but in the face of
an appropriate history, a blinded rechallenge with encapsulated suspects
could be useful.  Renal insufficiency and hyperbilirubinemia can cause
pruritis, but they should not be subtle.  Pruritis can be the presenting
symptom for primary biliary cirrhosis.  Chronic sinusitis is a relatively
common, but usually overlooked, cause of pruritis (and of urticaria).
Consider a parasitic disease, especially if there has been travel to
less-developed countries, use of water from a well or spring, a camping
trip, consumption of inadequately cooked meat, or (especially in the
southern states) walking barefoot outside.  Swimming in contaminated water
can cause intensely pruritic parasitic invasion of the skin, with or without
a noticeable rash, as can exposure to a freshwater fish tank.  A variety of
mites (harvest mites or "chiggers," various animal mites, and scabies), pre-
or post-eruptive shingles, and psoriasis can be causes of mysterious intense
pruritis, but a history of a rash is usually easily elicited, in the absence
of immunosuppression.  Fungal infections of the skin are not always
recognized for what they are.  Ichthyosis causes skin changes that should be
obvious, even if their identity is not.  Once pruritis occurs for any
reason, scratching can induce lichenification, which then perpetuates the
pruritis, but this is usually localized and easily detected.  Mycosis
fungoides and some other oncologic diseases can cause pruritis.  Carcinoid
syndrome, the mast cell dyscrasias, eosinophilic granulomatosis, and
histocytosis X are rare causes of systemic pruritis that may not result in
rashes.  Although I disagree with most of the diagnoses of neurodermatitis
and formication that I have encountered, these entities should be kept in
mind.  Consider screening with a CBC for eosinophilia, a CMP, and even serum
and 24-hour urine histamine levels.

I hope that this helps.

M. Shank, M.D., Ph.D.
Diabetes and Metabolism Special1st Care (sm)
715 W. North St.
Lima, OH  45801
email @ redacted

-----Original Message-----
From: email @ redacted
[mailto:email @ redacted]On
Sent: Wednesday, October 30, 2002 06:22
To: email @ redacted
Subject: Re: [IPm] Pruritis with Humalog and Novolog

george mcknight wrote:

>Any suggestions:
>40 y.o. Male, type I DM X 10 years.  Humalog pump x 2 years with no
>problems.  Developed severe pruritis, no rash, no site problems.  Resolved
>at once on Humilin-L injections.  Converted to Novolog pump therapy for 6
>months with no problems, then intense pruritis.  Again, no urticaria or
>problems. Resolved with Humilin-L injections and discontinuation of pump.
>Is this an allergy to insulin analogs, or to m-cresol preservative ?  How
>does one test for this?  Can this be a true allergic response in the
>of urticaria ?
>Tip McKnight
>Insulin-Pumpers website http://www.insulin-pumpers.org/
>For subscribe / unsubscribe information,
>send the next two lines in a message
>to the e-mail address: email @ redacted
Insulin-Pumpers website http://www.insulin-pumpers.org/
For subscribe / unsubscribe information,
send the next two lines in a message
to the e-mail address: email @ redacted
Insulin-Pumpers website http://www.insulin-pumpers.org/
For subscribe / unsubscribe information,
send the next two lines in a message
to the e-mail address: email @ redacted