The patient is a 43
yo Hispanic female. with several months of bleeding gums, sloughing tissue, and
generalized oral pain. She is otherwise
healthy and takes no meds or supplements.
She has no skin or vaginal lesions.
Lab: Normal
CBC and metabolic panel.
Her oral surgeon did a biopsy biopsy of normal mucosa adjacent to sloughing attached gingiva on anterior mandible and sent this for direct immunoflouresence (DIF).
Her oral surgeon did a biopsy biopsy of normal mucosa adjacent to sloughing attached gingiva on anterior mandible and sent this for direct immunoflouresence (DIF).
Clinical Image:
Path:
H&E:
Acantholysis
DIF: Intercellular deposition of C3 and IgG.
Diagnosis: Pemphigus vulgaris
Questions:
This patient does not live close to an academic center and travel there would be difficult.
Does it make sense to initiate therapy with rituximab (if her insurance covers that) + prednisone. or should therapy be initiated with prednisone and conventional adjunctive added later if nexessary?
References:
Questions:
This patient does not live close to an academic center and travel there would be difficult.
Does it make sense to initiate therapy with rituximab (if her insurance covers that) + prednisone. or should therapy be initiated with prednisone and conventional adjunctive added later if nexessary?
References:
1. First-line rituximab combined with short-term prednisone
versus prednisone alone for the treatment of pemphigus (Ritux 3): a
prospective, multicentre, parallel-group, open-label randomised trial.
Joly P. et. al. Lancet.
2017 May 20;389(10083):2031-2040.
This is a paper by the French study group on autoimmune bullous
skin diseases.
CONCLUSIONS: 32.5% of our patients with moderate to severe
pemphigus vulgaris failed prednisone and traditional CAT treatment and required
rituximab therapy. Rituximab reduced the monthly prednisone intake in these
patients by 73%. This suggests that a subset of patients with moderate to
severe pemphigus may benefit from early institution of rituximab therapy.
Rituximab significantly reduces the monthly prednisone requirement among
CAT-resistant pemphigus vulgaris patients to levels on par with CAT-responsive
patients.
2. Comparison of rituximab and conventional adjuvant therapy
for pemphigus vulgaris: A retrospective analysis.
Agarwal A, Hall RP 3rd, Bañez LL, Cardones AR.
PLoS One. 2018 Sep 25;13(9):e0198074. Free PMC Article
CONCLUSIONS: 32.5% of our patients with moderate to severe
pemphigus vulgaris failed prednisone and traditional CAT treatment and required
rituximab therapy. Rituximab reduced the monthly prednisone intake in these
patients by 73%. This suggests that a subset of patients with moderate to
severe pemphigus may benefit from early institution of rituximab therapy.
Rituximab significantly reduces the monthly prednisone requirement among
CAT-resistant pemphigus vulgaris patients to levels on par with CAT-responsive
patients.
3.
3.
JAMA Dermatol. 2015 Aug;151(8):878-82.
Intralesional
Rituximab in the Treatment of Refractory Oral Pemphigus Vulgaris.
Vinay K, Kanwar AJ, Mittal A, Dogra S, Minz RW, Hashimoto T.
JAMA Dermatol. 2015 Aug;151(8):878-82.
Abstract
IMPORTANCE:
Oral lesions of pemphigus vulgaris are usually recalcitrant
and respond slowly to treatments. Corticosteroid injection is considered to be
the most effective local treatment in oral pemphigus vulgaris. However, intralesional
corticosteroids are not effective in all remnant lesions. In 3 such patients
with pemphigus vulgaris, we evaluated the utility of 2 injections (on days 1
and 15) of intralesional rituximab, 5 mg/cm², in terms of accelerated healing,
limitation of the use of systemic immunosuppressants, and reduction of their
adverse effects.
OBSERVATIONS:
Three patients (1 man and 2 women) received 2 doses of
intralesional rituximab in March and April 2013. All 3 patients responded to
the treatment. In patients 1 and 2, the objective severity score was reduced to
0 at the final visit from a baseline score of 4 and 5, respectively (range,
0-11). The subject severity score in these patients was reduced to 1.0 and 0
from a baseline score of 22.0 and 22.5, respectively. After clinical remission
was achieved, patient 3 developed a relapse of mucosal lesions. At the final
visit, all of the patients were satisfied with the treatment, with a mean
satisfaction score of 8 (maximum score, 10). We found a marked decline in the
CD19 cell count from a pretreatment mean count of 287 cells/µL to 6 cells/µL on
day 15 after a single intralesional rituximab injection. Adverse events were
limited to local pain in 1 patient.
CONCLUSIONS AND RELEVANCE:
Intralesional rituximab administration lacks the adverse
effects of intravenous administration. This method reduces the amount of drug
administered and therefore is less expensive. Encouraging results from our
study should prompt further evaluation of this novel route of rituximab
administration in patients with refractory oral pemphigus vulgaris.
Robert Shapiro: "No steroids , just rituximab and IVIG"
ReplyDeleteKhalifa Sharquie, Baghdad: Steroid and azothioprine saved the life of hundreds of patients with pemphigus over years as the disease is endemic in Iraqi population affecting young patients .Rutiximap is rarely available and expensive.
ReplyDeleteThanks for the consultation.
ReplyDeleteI'd start with oral washes with topical steroid, and azathioprine PO,
Richard Sontheimer wrote: "Since moving to Utah, I haven’t cared for many autoimmune blistering disease patients since we have several other people in our department who have a subspecialty interest and do research in this area, including our departmental Chairman, John Zone. On several occasions John has told the derm faculty that if he ever personally develops pemphigus he wants to be treated with rituximab first rather than prednisone. I think he was half joking about this but also half serious.
ReplyDeleteIt is my understanding that while some pemphigus patients respond extremely well to rituximab-induced B-cell depletion, others do not. The same has been true for systemic LE and dermatomyositis. It has been difficult to understand these marked inter-individual differences in clinical response rates.
I gave a grand rounds presentation in our department this past summer during which I presented a review of some preliminary data from the rheumatology literature suggesting that the clinical impact of rituximab on otherwise-refractory SLE nephritis might be markedly enhanced by sequential belimumab (Benlysta) subcutaneous injections following B-cell depletion with IV rituximab. The rationale is that belimumab might prevent the rebound wave of B-lymphocyte stimulator (BLyS) (syn. B cell activating factor [BAFF]) that occurs after rituximab induced B-cell depletion. Thus, this combination therapy might produce a longer period of B-cell-induced autoimmune suppression. There are now ongoing clinical trials to formally test this hypothesis in SLE nephritis. I have attached a PowerPoint file containing the relevant slides from my Grand Rounds presentation.
If this proves to be true it may have a value other B-cell mediated autoimmune disorders including dermatomyositis and pemphigus/pemphigoid.
All things being equal (including affordability of the rituximab), I would strongly consider starting the VGRD pemphigus patient on rituximab and prednisone with the idea of tapering the prednisone to a safe low dose range as the rituximab induced B-cell depletion kicked in clinically."
Henry Foong, Ipoh, Malaysia. wrote:"I had a similar patient in 2018 referred to me by an ENT surgeon. A chinese woman in her 50s with recurrent ulcerations and blisters in the buccal mucosa esp upper hard palate. Biopsy confirmed pemphigus vulgars. I treated her with oral prednisolone and weekly methotrexate and she achieved remission. Now she is on prednisolone 10mg daily and methotrexate 7.5 mg weekly with topical triamcinolone gel when necessary. I have stopped using azathioprine as the response is slow and inadequate. I find methotrexate much better in terms of efficacy. Rituximab is too expensive in our practice and not sure if warranted in such limited oral disease."
ReplyDeleteJorge Roman, NYU Skin and Cancer: "What's interesting about NYU is that the treatment would vary depending on which attending the patient saw. Some are a little more conservative with oral steroids while others have a lower threshold. The burden of pemphigus on the patient is an important factor to consider. If she's unable to eat comfortably and losing weight, prednisone might be more favorable at least in the interim while rituxan gets approved. If rituxan isn't an option, cellcept seems to be the go to choice for most of the faculty here. If a patient does not get improvement with max dose of cellcept, adding on dapsone usually does the trick. IVIG can also be considered but given the patient is far from an academic center, likely not feasible for her."
ReplyDeleteThis comment has been removed by the author.
ReplyDelete