When A Patient Has A Post-Op Bullous Reaction

Pages: 20 - 23
William Fishco, DPM, FACFAS

A 39-year-old female presented to my office with a chief complaint of pain surrounding both great toe joints. She had symptoms for five to six years. Prior treatment measures included wearing wider shoes and bunion pads. Her main area of pain was on the medial bony prominence at the great toe joint.

   Her past medical history was remarkable for depression. Daily medications included sertraline (Zoloft, Pfizer), fish oil, vitamin B12 and vitamin D. Allergies included an allergy to penicillin, which caused a rash but not anaphylaxis. Past surgical history included two Caesarean sections and excision of keloids. The patient was married, unemployed, a non-smoker and a mild drinker of alcohol.

   The podiatric exam revealed strong pedal pulses of 2/4 for the dorsalis pedis and posterior tibial arteries bilaterally. The capillary refill was less than three seconds to the toes. Her skin was warm and pink. The neurologic exam revealed symmetric deep tendon reflexes and epicritic sensation was intact to the level of the toes. There was no clonus or Babinski reflex.

   The dermatologic exam revealed skin temperature, texture and turgor within normal limits. There was no evidence of rash, edema, varicosities or a break in the integument. Her toenails were healthy. The orthopedic exam revealed symmetric, pain-free range of motion of the ankle and hindfoot. Gross visualization of her feet revealed mild to moderate bunion deformities with lateral deviation of the great toes. The range of the motion of the great toe joints was not painful. The dorsomedial eminence of the great toe joint was painful to palpate.

   Radiographs of her feet revealed a moderate underlying metatarsus adductus with mild to moderate bunion deformity. No acute fracture was visible. No underlying arthropathy was present.

   The patient elected to have surgery to address the chronic pain and deformity of her feet. She wanted to have surgery on the right foot first. Abnormal preoperative labs were remarkable for a mean corpuscular volume of 76.3 (normal values 81.0 FL-97.4 FL), a mean corpuscular hemoglobin of 24.8 (normal values 37.0 PG- 34.0 PG) and a red blood cell distribution width of 16.2 (normal values 11.7%-14.4%). Her remaining complete blood counts and chemistry profile were normal.

   I performed a traditional Austin bunionectomy with single screw fixation in a standard fashion. Due to the patient’s history of keloids, I used a minimal reactive suture. I closed the skin with a 5-0 Prolene suture in a running intradermal stitch, using Mastisol (Eloquest Healthcare) and Steri-Strips (3M) to reinforce the skin. Her surgery progressed without any technical difficulty or complications.

   The patient followed up in one week for her first postoperative appointment. She had been in moderate pain and described some itching on her foot. She self treated with diphenhydramine (Benadryl, McNeil Consumer Healthcare) and that did help. Clinically, her foot was very swollen and red. I was concerned about infection due to the bright red appearance of her dorsal foot. I cleansed the foot, wrapped it in an elastic compression bandage and instructed her to continue to elevate and ice the foot. She wore a pneumatic fracture boot for weightbearing as tolerated. I gave her a prescription for clindamycin (Cleocin, Pfizer) 300 mg #21, i PO TID. I advised her to return to the office in two weeks.

   I received a phone call from the patient two days after her initial postoperative visit. She noted that she was developing a blister on the top of her foot and having more itching and pain. I instructed her to return to the office the following day for evaluation.

   A large bulla was present in the interspace between the big toe and the second toe. I removed her Steri-Strips to inspect the rest of the surgical wound and found multiple small vesicles in the region of the Steri-Strips and to the periphery of the incision line. There was no evidence of purulence. I drained the bulla, which was flaccid and contained a serosanguineous fluid, but I left the roof of the blister intact. The area of erythema was localized to the surgical site. No ascending lymphangitis was present.

Key Questions To Consider

1. What are the differential diagnoses?
2. What is the diagnosis?
3. What features of this condition differentiate it from other conditions?
4. What is the appropriate treatment?

Answering The Key Diagnostic Questions

1. Cellulitis/abscess, pemphigus vulgaris, bullous pemphigoid, stasis bulla, cutaneous drug eruption and contact dermatitis
2. Allergic contact dermatitis
3. The erythema was well demarcated from the surface area in which I had applied Mastisol. The patient had a component of pruritus, which is not a symptom of infection. After drainage, the bulla did not have any purulence and the underlying dermis appeared healthy.
4. A tapered dose of oral prednisone (60/40/20/10/5 mg x three days each) and local treatment with topical Betadine (Purdue Products) to dry out the weeping bulla/vesicles, and triamcinolone (Kenalog, Bristol-Myers Squibb) 0.1% ointment on the rash.

A Closer Look At The Differential Diagnoses

This case illustrates a bullous reaction following podiatric surgery. The common differential diagnoses include cellulitis/abscess, pemphigus vulgaris, bullous pemphigoid, stasis bulla, cutaneous drug eruption and contact dermatitis.

   Pemphigus vulgaris is a dermatologic condition characterized by flaccid bullae of the skin and mucous membranes. The lesions are rarely pruritic and can be painful. The disease is an autoimmune disorder caused by antibodies attacking desmoglein 1 and 3 antibodies. The mean age of onset is typically between 50 and 60 years of age. The most common areas of predilection include the trunk, intertriginous areas, neck and head.

   Bullous pemphigoid is a condition that yields tense blisters. These blisters are usually on the upper arms and thighs, but are also visible on the hands and feet. The autoimmune disorder occurs in older people, who are usually in their 70s or older. The condition can be precipitated by medications including non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, furosemide (Lasix, Sanofi-Aventis), captopril (Capoten, Bristol-Myers Squibb) and penicillamine (Cuprimine, Valeant Pharmaceuticals).

   Stasis bullae are caused by prolonged swelling in an extremity. Oftentimes, there is associated stasis dermatitis, which will cause redness and scaling of skin. Stasis bullae are caused by excessive fluid pushing toward the surface of the skin, creating a pocket that manifests as vesicles or bullae. This condition typically occurs in patients who retain fluids due to congestive heart failure, kidney disease, liver disease, post-phlebitic syndrome of the leg, venous insufficiency or hypoalbuminemia.

   Cellulitis and/or abscess can occur after surgery. Even though the incident rate of postoperative infection is low, this is the most critical diagnosis to rule out. With abscess, blistering of skin can occur where infectious material (purulence) is trying to extrude from the body. Cellulitis is a common finding with infection causing redness and potential streaks along a lymphatic channel (lymphangitis). Patients with cellulitis/abscess would typically encounter more pain than one would expect after surgery. There may be accompanied systemic effects such as fever, chills and/or malaise. Itching is not a common element of infection. If you suspect an abscess, institute antibiotics for treatment and perform incision and drainage with lavage immediately.

   Cutaneous drug eruptions are a common cause of rash, itching and blistering of skin. Typically, drug eruptions occur seven to 10 days following administration of a drug. It can, however, take up to three weeks for a rash to develop. Medications that patients have taken for many years are less likely to be a source of the drug eruption. In some cases, a drug eruption can occur up to three weeks after discontinuing drug use (i.e. penicillin). The most common drugs that are associated with cutaneous drug eruptions include: antibiotics (especially penicillin-based drugs), NSAIDs, sulfa-based medications and anti-convulsants such as phenytoin (Dilantin, Pfizer). The classification of drug eruptions includes erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma and exanthematous pustulosis.

   Life-threatening reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma and angioedema.

   The classic appearance of erythema multiforme is a target or bull’s eye lesion. Patients with erythema multiforme generally have a prodromal period of flu-like symptoms before developing the cutaneous reaction. The most common area for erythema multiforme is on the hands and feet.

   Stevens-Johnson syndrome is typically associated with fever, malaise, myalgia, arthralgia and extensive erythema multiforme lesions on the trunk and face. Blistering may affect up to 10 percent of the patient’s body surface.

   Toxic epidermal necrolysis, which is the most severe reaction, can lead to bullous lesions comprising up to 30 percent of the patient’s body surface area. There is a high mortality rate approaching 40 percent.1 Typically, there is a prodromal period of nausea, chest pain, fever, malaise, sore throat and conjunctivitis. In about half the cases, there is oral involvement.

   Contact dermatitis is a dermatologic condition in which an inflammatory reaction occurs due to direct contact of a substance. There are two types of contact dermatitis. Irritant dermatitis is the most common type and is typically caused by acids, alkalies, fabric softeners and solvents. Clinically, irritant contact dermatitis generally looks like a sunburn.

What You Should Know About Allergic Contact Dermatitis

Allergic contact dermatitis is caused by exposure to a substance to which the body has sensitivity or allergic reaction. The common culprits causing allergic contact dermatitis include tape and adhesives; topical antibiotics (especially neomycin); fabrics; metals (nickel); rubber/latex gloves; plants (poison ivy) and fragrances in perfumes, soaps and lotions.

   The typical rash that occurs from allergic contact dermatitis includes redness of the skin as well as vesicles that weep and crust. Conversely, irritant dermatitis often appears as red, dry, cracking of skin (fissures).

   The case presented was a classic example of allergic contact dermatitis to Mastisol. Clinically, the patient developed a flaccid bulla and vesicles on an erythematous base. The erythema was well demarcated not from the Steri-Strips but rather the surface area that had an application of Mastisol. Even though I was concerned about cellulitis and possible abscess, the patient had a component of pruritus, which is not a symptom of infection. Furthermore, when I drained the bulla, there was no purulence and the underlying dermis appeared healthy.

   Most of the autoimmune bullous skin eruptions occur in older adults with associated oral lesions. This patient did not have any systemic manifestations of fever, chills, malaise or flu-like symptoms, which ruled out many of the cutaneous drug reactions.

In Summary

This patient developed an allergic contact dermatitis from Mastisol, which I treated successfully with a tapered dose of oral prednisone 60/40/20/10/5 mg x three days each. Local treatment included topical betadyne to dry out the weeping bulla/vesicles. Once the lesions were dry, I had her use triamcinolone (Kenalog, Bristol-Myers Squibb) 0.1% ointment on the rash. She ultimately responded very quickly to this treatment and all evidence of the rash was gone in two weeks. Luckily, she did not develop a keloid on her surgical scar, which was my main concern while planning surgery.

   Dr. Fishco is board-certified in foot surgery and reconstructive rearfoot and ankle surgery by the American Board of Podiatric Surgery. He is in private practice in Phoenix. He is also a faculty member of the Podiatry Institute.

   Dr. Fishco pens a monthly blog for Podiatry Today. For more info, visit www.podiatrytoday.com/blogs/william-fishco-dpm-facfas .

1. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008; 58(1):25-32.


In my humble opinion, surgery on this patient should have been deferred pending hematology consultation.

The patient showed a microcytic anemia preoperatively yet nothing was presented to indicate that this systemic condition — which in and of itself could cause postoperative healing problems — was addressed with proper referral, determination of the underlying cause and proper treatment. This could be the tip of an iceberg or it could be nothing.

In either event, while it cannot be said with 100% accuracy that the postoperative allergic reaction was related to the anemia, had the allergic reaction sufficiently compromised the surgical site to allow for infection, this case would have been reported with a different outcome.

An infected surgical site compounded with an allergic reaction would have been challenging to say the least. But an infected surgical site compounded with an allergic reaction AND an anemic patient? This would have been a VERY challenging case.

The systemic demands on a patient in the postoperative period should never be underestimated. Surgery is a stress and in all likelihood, the patient's cortisol production will go up. Cortisol has systemic immunosuppressive effects. This is just one of the postoperative systemic effects of surgery to expect. The administration of drugs further taxes the patient physiologically for all drugs, in greater or lesser degrees, are poisons. The body has to process them and eliminate them.

Then there are more postoperative reactions. Given these, why perform ELECTIVE surgery on an already potentially compromised host? First and foremost, we are bound to do no harm. In the best interests of the patient, upon discovery of the blood anomaly preoperatively, the patient should have been appropriately referred and surgery withheld until competent medical clearance was established. This is elective surgery and as such, we have the luxury of putting it off until a patient's questionable condition has been addressed and either stabliized or otherwise handled. Why perform preoperative testing if not to protect the patient? And upon discovery of an anomaly, why not address it first and operate later? Again, this is my humble opinion, tempered with over 30 years of clinical experience.

Thank you for your comment. The most common cause of microcytic anemia in a 39-year-old female is iron deficiency secondary to menses. She had no history of chronic diseases. If I sent her to hematology for the minor lab abnormalities, I would feel like I am treating her labs. Moreover, she would probably have more tests done and in the end, she would be given an Rx for iron.

Thank you for your response. However, I stand by my comments. Your statements of "...microcytic anemia in a 39-year-old female is iron deficiency secondary to menses ... no history of chronic diseases ... treating her labs ... likely be given an Rx for iron ...," are presumptive and beyond the scope of the practice of podiatric medicine and surgery.

When any physician takes on a patient, we take on the whole person. If something happens to them, then for that patient its 100% and telling that patient after the fact that you proceeded based upon the "odds" of what the most common cause of their complication is is telling them that you gambled with their life. That she had no history of chronic disease means what? Were these preoperative findings indeed the hallmark to her first chronic or acute disease? This is unknown until proven otherwise. We do not treat labs, per se, but we must not ignore them and presume them to be what we want them to be because we are either anxious to operate or under patient pressure to do so. That would be akin to "junk science".

Case in point. I recently had a patient with chronic peroneal tendonosis confirmed by MRI that I was considering treating with PRP. He was a healthy, 46-year-old male who was not obese. He was a "perfectly" healthy person. I ran full bloods & urine including PSA. His PSA came back only slightly elevated. I referred him to his medical doctor. Long story short: He had malignant prostate cancer but it was caught early. The patient credits me with saving his life.

Over my 30 years of clinical experience, I have had several incidents of seemingly innocent preoperative findings that turned out to be much more. There was a 32-year-old female who was perfectly healthy and had no history of chronic disease. Her foot had a "fungus" that she stated had been treated in the past with creams but "it comes back ... I just deal with it." Her preoperative labs were ALL normal. But to be safe, I biopsied the "rash". Result: mycosis fungicides.

This condition is more common in men, is uncommon to present until the 5th decade of life, and comprises only 5% of all lymphomas. Had I treated her on the "odds" that her rash was "nothing," I would have done her a severe disservice. She is very thankful. While it is not curable, if it was untreated, it can have dire consequences including a spread to lymph nodes.

I have also discovered preoperatively hepatitis A and anemia in patients with slightly abnormal findings but a high index of suspicion and interest first in the patient's overall well-being. This lead to uncovering the underlying disease process and providing good service and competent referral to these patients. I'm not blowing my own horn, just relating what I've experienced.

In the presence of abnormal preoperative labs, repeating them to confirm the abnormality and rule out lab error can be ordered.

We are not trained in the intricacies of hematology. Blood analysis is evolving everyday revealing a dizzying maze of information. Leave that analysis to hematologists.

Further, you stated that following surgery, you scheduled the patient for her first post-operative visit in one week. In my humble opinion, this is too long. The first postoperative complication any surgeon is on the lookout for is infection, which hopefully shows its first signs in 48-72 hours. I was trained to see my post-ops in that time frame. A fresh dressing applied after removing a bloodied, compressed dressing is most welcomed by patients, increasing their comfort and confidence in their physician that they are being watched and taken care of. More importantly, it affords us the opportunity to inspect and head off something before it become a fulminating problem, such as what you experienced. Patients trust us and usually will not call for an unscheduled appointment unless in great discomfort, which again, you experienced.

After the first postoperative visit, when you documented a potentially important complication and prescribed an antibiotic, the next scheduled patient visit was ... in two weeks? In a patient with a documented postop complication, was this prudent? I would have scheduled to see that patient every 2-3 days to keep a close watch on the complication. Fortunately for you, the patient called you in two days, affording you exactly that opportunity.

One of my mentors, Stanley Kalish, DPM, gave me some advice I've never forgotten, that he'd learned from Marvin Steinberg, DPM: wisdom is the ability to learn from your own mistakes; intelligence is the ability to learn from the mistakes of others. If you could live long enough, you will learn all there is to know. But we don't. It is incumbent upon us to learn from the wisdom of those who have gone before us and make their wisdom our intelligence.

Overall, in my opinion, this case demonstrates an ill-advised pursuit to operate, presumption of the meaning of abnormal preoperative blood results, and too infrequent postoperative monitoring and management. You were fortunate this case didn't become your worst nightmare. Had this case gone to court, you would be hard pressed to defend your actions.

Thank you for submitting this case to the community for comment.

From medbc.com/annals/review/vol_9/num_3/text/vol9n3p168 dot htm :

"Recent studies suggest that mast cells participate in the pathogenesis of atopic and contact dermatitis, fibrosing reactions, bullous pemphigoid, cutaneous disorders, neurofibromatosis, wound healing, polycythemia vera, and psoriasis. ' An increase in the number of mast cells was observed in localized sclerodermia,' progressive systemic sclerosis,' and hypertrophic scars and keloids.1,1 Mast cell morphology was noted by Kischer and Bailey' in hypertrophic scars, mature scars and normal skin, and, some years later, mast cell analysis was also performed during the different stages of healing.'"

The above quote adds emphasis to this question: in a patient with a history of keloid formation, why use a topical skin adherent with its attendant possibility for cutaneous reaction?

The patient had already demonstrated a predisposition to cutaneous complication. Why challenge her skin with a substance that she could potentially be allergic to?

In such a patient, would it not be more prudent to avoid anything extra that could potentially become a problem later?

Hindsight is always 20-20 but this case did give warning: the history of keloids.

While, "...a minimal reactive suture ...," was used, "...due to the history of keloids...," showing your awareness for potential allergic reaction and desire to minimize it, why then did you use substances (Mastisol, Steri-Strips) topically?

Mast cells are mediators of allergic responses.

In a patient with already documented skin complication which histologically shows an increase in mast cells, would it not be wiser to limit the materials used in surgery to the absolute minimum and with little to no reactivity?

It looks like we can go round and round on this one. I appreciate your comments and we have all had similar cases that you illustrated. What I don't appreciate is your opinion as to whether I am practicing within the standard of care.

I always see my first post-op check up in a week unless it is a wound or an infection. My philosophy is different than yours. I would rather have my patient rest, elevate, and ice for a week rather than schlepping around 2-3 days post op and then have the fresh wound exposed to air. When I remove my bandage following a bunion surgery, there is typically a blood spot the size of a quarter on the the gauze square. I don't use tourniquets and when the skin is closed, there is no bleeding. Hopefully, Dr. Kalish taught you anatomic dissection and proper tissue handling so that you don't have to worry about hematomas and bloody bandages.

I have a special relationship with my patients that allows me to have them follow up in week or two as needed. I give them my cell phone number and I keep a close eye on them. If there is a problem, they will let me know. My patients don't want to come in every day or two unless it is really necessary.

This will be my last comment related to your original post. I am sure you would like to get the last word in so be my guest.

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