Given the lack of pollen at this time of year, all I have been seeing is hives. Curious as to everyone’s algorithms in terms of uncontrolled chronic urticaria. What is your stepwise progression?
My typical steps…
Step 1: Antihistamine load ( start with once daily Zyrtec/Allegra, will escalate to 3-4x/day, Zantac 300mg daily, with hydroxyzine 50mg tid)
If that fails…
Step: 2: Dapsone 100mg daily x 6-8 weeks or Plaquenil x 6-8 weeks
When* that fails….
Step 3: Cellcept 1gm twice daily (I know many use cyclosporine, but am more wary of those side effects)
I have previously reserved Xolair for the last step, but am thinking about making it step 2.

Step 1: high dose 2nd gen antihistamine, usually Zyrtec. Titrate to effect. I don’t bother with Zantac or singulair as the studies dont seem convincing that they help.
Step 2: usually Xolair. Alternatives that are well tolerated are dapsone and 3-5 mg/kg/day cyclosporine.

I have seen excellent results from add-on montelukast in select patients. If they fail consistent triple regimen, it’s off to dermatology for consideration of third line Rx. I just don’t have the time or energy to prescribe poisons for hives!
Just got back from the ACAAI meeting. Sulfasalazine is being used in place of cellcept or cyclosporine now because: A. It is less toxic and B. It is highly effective in over 80% of patients. The dosing is sulfasalazine 500mg q day for 3 days, then BID x 3 days, the 1000mg BID. One hepatic panel one month in is sufficient and then “periodically” which by consensus, was about every 6 months while on sulfasalazine. I will say, I just switched a difficult to control hive patient onto it from cyclosporine and she responded better than anything else we have tried. I know it is an n of 1, but still…
Chronic Urticaria is defined as hives which recur regularly for a period of at least four weeks. Unlike acute urticaria, it is rarely associated with allergy. In most cases, chronic urticaria is an autoimmune condition caused by IgG autoantibodies directed against the high affinity IgE receptor of mast cells. Rarely, however, it may be associated with underlying conditions such as occult malignancy (particularly hematologic malignancy), liver disease, thyroid disease (particularly with the production of anti-thyroid antibodies) or other autoimmune diseases such as lupus. The extent of the laboratory work-up for this condition has been debated for some time. I usually do the following: CBC with differential, TSH, anti-thyroglogulin antibody, anti-thyroid peroxidase antibody, AST, ALT, GGT, ANA, rheumatoid factor, sedimentation rate. Of course, a good history and physical exam is also important. What is the extent of the laboratory work-up which you use in patients with chronic idiopathic urticaria?

As a board certified allergist, I see a lot of patients with chronic idiopathic urticaria and angioedema. I have found that in most patients, especially those with a significant angioedema component, a combination of cetirizine (Zyrtec 10 mg) and montelukast (Singulair 10 mg) is effective prophylaxis. An early published study on loratidine and montelukast in combination showed no added efficacy, however the data on montelukast and cetirizine is scanty. Loratidine does not have significant antiinflammatory properties, unlike cetirizine which inhibits eosinophil migration and activation. While I have not conducted a controlled study, I would estimate that 80% of my chronic urticaria/angioedema patients are better controlled on the combination. Those that fail treatment usually require multidrug regimens, such as adding a second or third antihistamine or even prednisone.

Generally, chronic idiopathic urticaria (I assume that is what you mean by stable urticaria) stays the way it presents. It is unusual in practice to cause angioedema as well. I would suggest, if possible, any chronic urticaria patient be evaluated and followed by your local allergist as there are a variety of treatment options available these days. Also, Xolair should be getting FDA approval for chronic urticaria later this spring, which will add another treatment option as well.

Send him to another allergist or dermatologist. The biggest mistake made is taking whatever medicine PRN. It must be taken regularly. A detailed history is important. Physical urticarias like dermographism are also common. More labs like anti thyroid antibodies, H. pylori, autologous serum transfer test, ANA, etc. I tend to add Doxepin 25mg hs or Periactin 4mg hs. PO steroids in higher and longer doses are needed to calm it down. Remember once it is chronic, in only 5% a cause is found. The good news is the hives will eventually go away. Good luck.

Not all chronic hives are idiopathic. The term idiopathic presumes you have ruled out common causes. If a patient with chronic urticaria is atopic, it helps to know that. I have the patient do a standard elimination diet for one week first, to see if there is any reduction in the hives, or need for medication. Sometimes this helps the patient to see that the hives are not idiopathic, but are, in fact, due to chronic ingestion of a staple food to which they are allergic. My own husband, who is very atopic, has suffered from chronic hives for over 3 years. I tested him at the onset and did not find the cause, but 4 months ago, his hives progressed to include asthma, and we had to detour to my office for epinephrine. The next week, I retested him and found a 40mm wheal to corn. With corn avoidance, the hives disappeared. Now, they mainly appear if he eats a hamburger or other bread, because most bread contains corn syrup. Most patients who come to me with hives want allergic causes ruled out. After this is done, along with antithyroid antibodies and ANA, they have peace of mind that we really have to work on their regimen. Then they are more willing to try regular meds. Interestingly, a significant number can be managed on diphenhydramine and do not find it sedating. Others require mixes of fexodenadine and cetirizine or desloratidine in order not to be sedated. I have one patient who did not respond to antihistamines well at all, and does miraculously well on colchicine, .6mg one daily. I use a lot of very low dose doxepin also. 10 mg is the lowest capsule size, but patients can titrate down using liquid. The goal is control of symptoms with no or minimal sedation. One mg of doxepin is equivalent to 775mg diphenhydramine (Sullivan, TJ circa 1981). Biggest problem with doxepin is wt gain. I had a patient once gain 40 pounds on it, despite cycling 10 miles a day. As soon as he stopped it, the wt started to come off.

I have occaisionsally biopsied the lesions and have picked up 7 cases of urticarial vasculitis. On two occaisions the patient had systemic mastocytosis with significantly elevated total serum tryptase levels. Other areas to explore which may be helpful are the sinuses as chronic sinusitis has been shown to cause CIU. Another patient had an infected distal fistula secondary to a surgical debridement of a leg wound. Once the infected tract was sterile, the hives abated.
Did this patient have any dental work prior to the onset?
How about travel?
Sometimes parasitic infection is not reflected in blood work and if the index of suspision is high enough, one can ask for a purged stool specimen which has a higher yield than a routine collection.
All in all I’ve found a combo of Zyrtec 10mg @ hs and Ranitadine 150mg, 2-3x/day helpful.
On a rare occaision I’ve added montelukast with marginal resposes but a good safety profile and low reports of untoward effects.
Lastley, ETOH, intense exercise, anxiety, antihypertensive medication and ASA/NSAID use should be queried as well.
Good luck! I’d rather do root canal on a pit bull!
jmkhrk

Your husband clearly has chronic urticaria. The fact that cetirizine (Zyrtec) nearly fully controls his symptoms suggests that it is “simple” (meaning that the welts are due to oozing of fluid to the interstitial space) and not an inflammatory exudate. The bad news is that >80% of CIU are truly idiopathic. The current practice guidelines for the management of CIU even deter physicians from doing any blood work beyond basic CMP, CBC and ESR. The bad news – may need to take cetirizine for a long time (daily) for at least 2-3 months, then try QOD, if tolerated, slowly increase the interval and stop, IF POSSIBLE. To reduce dermatographism – warm (not hot) showers, mild soaps such as unscented Dove or Vanicream, patting dry (NOT RUBBING), use a hypoallergenic emollient such as Vanicream, Vaniply (you can try to get samples from the company in Rochester, MN) or CeraVe. The disease is frustrating to patient and physician. He is lucky to be controlled by cetirizine 10mg (may dubble uyp, if necessary). I have patients on dapsone, cyclosporine and tacrolimus for CIU!

See an allergist if you want to find out what is causing the hives. While waiting, try the usual meds, none of which are FDA approved for urticaria except for the antihistamines. Dapsone, montelukast, Plaquenil, etc have all been used off label for urticaria. I usually spend a full hour getting a detailed history and exam in chronic urticaria. There are guidelines floating around right now, but for chronic uritcaria most of the data is not very evidence based, since it is based on retrospective series with small prospective series. Unfortunately, the guidelines have been heavily influenced by the immunologist and rheumatologists, and not by practicing allergists. For example, allergy skin testing and immunotherapy for CU is poo pooed, ignoring double blind placebe controlled trials of allergy immunotherapy for chronic uriticaria done in Egypt. Many of the classic studies are ignored, since they do not show up on medline searches, since they predate the digital records. The study on house dust mite immunotherapy for CU was a good study done in the 1980s and published out of Egypt, and I have never seen it cited. I do routinely screen for allergy and find clinically significant allergy at least 40% of the time. Most of these patients have other atopic disorders such as rhinitis. Physical urticarias are also often missed but can be diagnosed by provocative testing.

One of the allergist I work with always check for H.PYlori , one patient got better after treatment.
Singulair may help.

I incorporated sulphasalazine (or preferably olsalazine if insurance covered) 10 years ago, but after so many patients not a single one responded and so I have abandoned this. Similarly, H2 antihistamines have rarely if ever been worthwhile.
Montelukast has saved numerous patients from having to advance to more aggressive therapies. It’s now inexpensive and worth a 1- to 2-week trial (don’t need longer than 1 week to determine efficacy, really). Efficacy for antihistamine non-responders can be up to 40% of patients in my office who try it. The response can be quite nice and dramatic in many of those cases. Another ‘conservative’ therapy is doxepin, which is among the highest potency antihistamine. Mirtazapine is similarly high potency but has the rare blood dyscrasia risk. Also, doxepin has some other potentially useful receptor effects.
Colchicine can be effective sometimes; efficacy should be apparent by 1 to 2 weeks, or else move on. Mycophenolate has a lower percentage response rate (maybe 40% of my refractory patients?) than cyclosporine (something like 60% will respond). Both will work rapidly and so don’t need to be dragged on for weeks and weeks before efficacy is apparent. Dapsone was mentioned already and also works rapidly in most patients; a 4-week trial should suffice. Hydroxychloroquine is the slowest acting for all its indications (except perhaps malaria, although one could question if that is a valid indication anywhere in the world any longer); 4 or 5 weeks would be necessary before evaluating efficacy. One could start HCQ concurrently with a rapid-acting agent. If response occurs soon, then it was the mycophenolate (or whichever), whereas response toward the end of the month would be attributable to the HCQ.
There are numerous other possibilities, but I have only had to consider moving onward to omalizumab on a solitary occasion, whereupon it actually failed.