Suture Hypersensitivity

Etiology

Suture material placed in human tissue represents a foreign body and provokes an immunologic response. The tissue response depends on the suture material (absorbable versus non-absorbable, synthetic versus biologic), the type of tissue receiving sutures, and the immune system. Inherent properties of absorption, filament number, size, and tissue reactivity are among the features of suture material implicated in the tissue response. The innate immune system, the adaptive immune system, or a combination thereof may drive the response. The most frequently implicated agents are macrophages, responsible for the cell-mediated response, commonly called type IV hypersensitivity reaction.

To explain suture hypersensitivity, what constitutes a normal tissue response to the presence of foreign material must be established. Sutures serve as a persistent, or even non-degradable, antigen, which elicits a macrophage-dominant reaction over weeks. Activated macrophages often morphologically change to epithelium-like cells, epithelioid cells, or histiocytes. Granuloma formation constitutes the aggregation of the epithelioid cells with surrounding lymphocytes. Such reactions are called granulomatous inflammation, related to strong T-cell activation and cytokine production. Foreign bodies that activate macrophages without an adaptive immune response can also elicit this reaction.

Absorbable sutures depend on the tissue response for their timely dissolution. Suture hypersensitivity is related to the duration of suture absorption, developing such a reaction at the end of the absorption process. The sutures' diameter might be critical in this process.

The tissue response elicited by suture material is a specific case of this generalized form of inflammation. The reaction can be broken down into acute and chronic phases. At least the acute response of tissues to suture is the same for all sutures during the first 5 to 7 days.[3] A postoperative inflammatory reaction and acute suture hypersensitivity are seen within 48 hours after the operation.[4] For absorbable sutures, observable differences in the tissue reaction arise after the acute phase once absorption begins. Catgut appears characterized by a thin capsule of connective tissue and a few histiocytes and lymphocytes, characteristic of any monofilament suture.[3] After absorption, the site is marked by a collection of monocytes with characteristic brown, foamy cytoplasm.[3] Catgut suture reaction depends on the period of the suture absorption and is mainly histiocytic in type. Instead, non-absorbable sutures are encapsulated by a rim of connective tissue with surrounding histiocytes, giant cells, and lymphocytes. This is most commonly encountered with silk and cotton sutures, less often with dacron, and least with nylon and wire.[3] 

In contrast, non-absorbable sutures remain in tissues indefinitely and exhibit a different tissue reaction. Buried silk produces an initial prompt tissue reaction consisting of mild edema and a collection of polymorphonuclear leucocytes around the suture. By the third day, a few fibroblasts are seen, and the intensity of leukocyte infiltration decreases. As the process continues, there is a gradual increase in monocytes, giant cells, and round cells and a decrease in polymorphonuclear cells. Fibroblasts penetrate between the silk fibers and eventually form a fibrous capsule around the suture material.[5] 

The reactions to silk may be divided into 2 major types. In the first and most frequent, the suture remains tight and is surrounded by a fibrous tissue capsule with variable thickness. Also, it is accompanied by a layer of histiocytes from 1 to 3 cell layers deep. Giant cells and lymphocytes vary in both occurrence and number. In more cellular reactions, capillaries may be prominent. In the second type of response, the capsule is present, but fibroblasts and histiocytes invade the interstices of the suture. In rare instances, the response appears much like granuloma.[6] A foreign body granuloma is a reaction to exogenous or endogenous materials that are too large to be ingested by macrophages.[4] Nylon is the least of all sutures examined for tissue reactions. All specimens contained the monofilament type and were surrounded by a narrow, compact, fibrous tissue zone. Histiocytes adjacent to the suture occur occasionally; giant cells rarely. No fragmentation of the suture is seen.[3] 

The extent of the tissue reaction also depends on the tissue receiving the suture material. Bladder lumen exposure with silk and mersilene sutures produced significant tissue reactions and stone formation. In comparison, with monofilament polypropylene sutures, this reaction wasn't present. Plain catgut produced the least tissue reaction.[7] Lower degrees of foreign body reaction, inflammation, and stone formation were encountered when using 4/0 polydioxanone.

The development of a foreign body granuloma may be associated with an immunoreaction of macrophages.[7] A giant cell, an inflammatory reaction to foreign material, is thought to underlie the various clinical manifestations of suture hypersensitivity.

Epidemiology

Tissue reactions to the suture material are rarely reported. The immune status of the recipient plays a role in the immunologic response to the suture antigen. However, people with a predisposition to allergies and autoimmune diseases are more likely to develop hypersensitivity reactions. Conversely, immunosuppressed individuals may be less likely to develop hypersensitivity. In 1 study, suture specimens were obtained from 12 renal transplant patients. All were receiving azathioprine and, most of them, steroids. Catgut, silk, nylon, and dacron were examined. The transplant had been less than 30 days earlier in 4 patients and ranged from 2 months to 5 years in the others. The remarkable finding was the minimal response, either fibroblastic or histiocytic, to the sutures. In some sections, the stitches appeared to have displaced adjacent healthy tissue without any cellular response.[3]

Chronic irritant dermatitis, allergic contact dermatitis, and contact urticaria are among the responses related to suture reactions. Suture materials related to such responses are silk, catgut, and chromicized catgut. Such reactions are less common in synthetic absorbable sutures such as polyglactin 910 and poliglecaprone 25. The risk of allergic reaction is low in the case of non-absorbable stitches, such as polyamide 6/6 and nylon, both containing the monomer e-caprolactam. Hypersensitivity reactions have been reported in cases where polypropylene and sterilized sutures with ethylene oxide and triclosan were used. The addition of dye for coloring sutures has also been reported as a cause of hypersensitivity.[2]

Other materials related to hypersensitivity reactions are acrylic resin, cyanoacrylate, and 2-octyl cyanoacrylate. These materials are commonly found on adhesives, plastics, paints, inks, and topical skin adhesives. In the surgical setting, acrylates are found in adhesives and surgical strips for wound closure. Other causes of prior sensitization with acrylates are sculptured nails and bone and dental cement. This increases the risk of hypersensitivity reactions. Other allergens commonly found in adhesives besides acrylates are colophony, abitol, abietic acid, benzoyl peroxide, rubber accelerators, and antioxidants. Cases of hypersensitivity reaction while using a hydrocolloid dressing are due to colophonium.[2][8]

Silk, when compared to catgut, is not only cheaper but is also more easily sterilized.[2][7][2][8] Silk sutures react less with tissues and result in more forcible wound closures.[2][3][2][8] Delayed silk suture allergies are rare. Asthma, interstitial cystitis, and necrotizing granulomas are related to delayed silk allergies. Removing the sutures can eradicate the allergy.[9]

Vicryl sutures are among the preferred sutures of clinicians due to their low antigenicity and sparse inflammatory infiltrates. Vicryl suture hypersensitivity is very rare. However, cases of suture allergies have been reported as pruritus, edema, pain, and seroma formation. Currently, no standardized method to test this reaction has been reported. Still, simply placing a single interrupted suture in the skin can evaluate a suture hypersensitivity.[10]

Pathophysiology

Cutaneous reactions are immune-mediated and related to different allergens, such as drug therapy or suture exposure. They can be divided into 2 categories: immediate-type reaction and delayed-type reaction. Immunoglobulin E (IgE) or T-cell delayed-type hypersensitivity mediates these reactions. The mechanism of IgE-mediated reactions is well-studied and understood. Meanwhile, the process in which delayed-type reactions occur in the skin is less well understood.

Allergic contact dermatitis is the most considered form of delayed-type hypersensitivity reaction, where sensitization to an allergen occurs. This condition is characterized by its acute phase in which erythema, vesiculation, and pruritus occur. The response is elicited by a hapten capable of interacting with cutaneous protein, which can be a chemical such as pharmaceuticals, sutures, and metallic compounds. Haptens are weak allergens requiring sensitization. Studies of the immune system reveal that a complex sequential series of events starts when the skin is in contact with the sensitizing agents.

These molecules aren't in direct contact with antigens. Instead, they bind with cellular or extracellular proteins before the immune molecules are aware. As soon as the hapten is in contact with the skin, they are taken via pinocytosis or endocytosis by the antigen-presenting cells in the skin. These antigen-presenting cells upregulate the expressions of surface molecules and cytokines. The major histocompatibility complex (MHC), and CD80, a costimulatory molecule, are good examples of such surface molecules. The primary antigen-presenting cells are the Langerhans cells in the dermis and epidermis. These cells are activated and migrate to the lymph nodes, carrying the hapten and presenting the antigen-MHC complex to a T-cell.

The activation of a T-cell requires 2 signals. The first signal is the contact of the peptide/MCH complex expressed on the antigen-presenting cell with their respective T-cell receptor. The second signal comes when the costimulatory molecules on the antigen-presenting cell interact with their respective T-cell receptors. Once the antigen is presented and the T cells activated, a transition from a naive T-cell to a memory T-cell or effector T-cell occurs. The population of T-cells with a skin-homing receptor could be created if the clonal expansion of suture-specific T-cells occurs. The second interaction of the suture with a T-cell receptor triggers a cascade reaction of cytokine secretion, cytotoxicity, or proliferation in reactive T-cell clones.

Keratinocytes are essential players in the immune responses in the skin, especially in the activation and prolongation of such a response. They can present antigens when inflammatory stimuli are present. Cytokines play an essential role in the cutaneous immune response. After being activated by an allergen, they are secreted by the skin cells, playing a crucial role in regulating cell killing. Cytokines, in combination with nitric oxide, secreted from keratinocytes and Langerhans cells, after exposure to allergens, have been considered to direct effector cells to the inflammation site. Examples of such effector cells are T-cells, macrophages, and neutrophils. Once the inflammatory insult occurs, tissue damage is caused. This tissue damage is believed to release pro-oxidant species, and these reactive oxygen species have been demonstrated to cause necrosis at a high level. On the contrary, low levels of reactive oxygen species induce apoptosis.[11]

History and Physical

Patients should be asked whether they have a history of allergies or prior reactions to suture materials. Observe the proximity of the patient's symptoms to previously operated sites. The list of relevant clinical entities includes but is not limited to, erythema, swelling, nodular mass, extrusion of the suture through an incision, pruritus, edema, pain, and seroma accumulation. Other possible findings are surgical adhesions, wound dehiscence, infection, intestinal obstruction along the line of suture material, and granuloma formation. When a patient is presented with wound infection or leakage, a suture reaction should be kept in mind.[6]

Evaluation

While the diagnosis is clinical, the distinction between suture hypersensitivity and the normal wound healing process may not be straightforward. However, this distinction's clinical relevance depends on the tissue reaction's severity and is warranted in the most severe cases.

Additional testing is usually not required except in a few select cases or scenarios. If confirmation is desired, skin allergen testing is sufficient. The test involves re-exposing the individual to the culprit suture material and observing for a reaction. The placement of a single interrupted suture exposes the content to the dermis, where the stitch is commonly placed, allowing for a response. In cases involving prior oncologic surgery, it may be necessary to perform a biopsy to rule out the recurrence of the malignancy.

Patch testing like the American Contact Dermatitis Society Core allergen series, the North American Contact Dermatitis Group patch test, and the thin-layer, rapid-use (TRUE) test are vital tools for recognizing the offending agent. None of the patch series screens for allergy to 2-octyl cyanoacrylate found in topical skin adhesives. In cases where such patches are unavailable, it has been suggested to consider testing with a suture through the skin versus placing the offending agent against the skin. A stand-alone, cutaneous test is recommended for suspected topical skin adhesives allergies.[2] 

For suspected cases involving deeper tissues, sonographic evaluation is useful. Suture granulomas in the abdominal ultrasound manifest as nodular hypoechoic lesions. A double hyperechoic line is a pathognomonic sign of this type of granuloma in the sonogram. Granulomas with clinical presentation can present with slight peripheral vascularization on ultrasound.[12]

Treatment / Management

The extent of tissue reactivity inherent to a given suture material is essential when selecting sutures. In general, tissue reactivity tends to be lower in non-absorbable sutures, moderate in synthetic absorbable sutures, and highest in sutures from a xenobiotic material source.

Treatment depends on the extent the hypersensitivity reaction complicates the healing process, its secondary complications, and how far from the initial procedure it arises. Successful treatment of chronic inflammation is achieved with surgical removal of the offending allergen. The healthcare team should start treatment with topical corticosteroid creams, oral antihistamines, topical immune response modifiers, and moisturizers. Systemic corticosteroids can be given in some cases.[6]

Differential Diagnosis

It is essential to distinguish a hypersensitivity reaction from common coexisting postoperative complications, such as scarring, bleeding, hematoma, infection, abscess, and wound dehiscence. In some cases, they may be secondary complications of a hypersensitivity reaction.

Suture hypersensitivity can mimic primary granulomatous disorders. It is crucial to distinguish between this foreign-body reaction and malignancy or wound infection recurrence. Differentiation from a malignant lesion or an infection can be achieved with a fine-needle aspiration wound culture with staining, respectively.[6]

Prognosis

Patient prognosis depends on the tissue involved and the severity of the suture hypersensitivity complications. In most circumstances, this is a self-limited condition without significant consequences.

Complications

The complications of suture hypersensitivity depend on the type of suture material used and the tissue being sutured. In general, the extent of inflammation, congestion, and foreign body reaction may complicate wound healing in any tissue. Amongst the complications are the following: postoperative adhesions, wound dehiscence, infection, and intestinal obstruction along the line of suture material to which the patient had been sensitized during a previous surgery. Suture materials increase the potential of bacterial colonization with low virulence in their sites and may lead to infections like Staphylococcus epidermidis infection. This reaction may serve as a lithogenic nidus in the urinary system, further complicated by obstruction and infection. In vascular and gastrointestinal anastomosis, suture hypersensitivity may cause the breakdown of such anastomoses.