Gram-Negative Folliculitis

Updated: Dec 14, 2022
  • Author: Mordechai M Tarlow, MD; Chief Editor: William D James, MD  more...
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Overview

Practice Essentials

Gram-negative folliculitis, first described by Fulton et al in 1968, [1] is an infection caused by gram-negative organisms. The infection may occur as a complication in patients with acne vulgaris and rosacea and usually develops in patients who have received systemic antibiotics for prolonged periods. [2] Gram-negative folliculitis should be considered in patients with acne who have a flare-up of pustular or cystic lesions and in patients whose acne is resistant to treatment. Gram-negative folliculitis may also occur in the setting of hot-tub immersion and in people infected with HIV. Note the image below.

Pseudomonas folliculitis. Courtesy of Hon Pak, MD. Pseudomonas folliculitis. Courtesy of Hon Pak, MD.

Signs and symptoms

A history is helpful in suggesting the diagnosis of gram-negative folliculitis.

Patients usually have been receiving a course of antibiotics for a prolonged period. Patients with gram-negative folliculitis may present with one of two histories.

A history of apparent acne, usually of the nodulocystic form, may be present. The acne has not been responding to antimicrobial therapy or other therapy. A history of acne that has responded well to therapy and suddenly flares may be present.

Because gram-negative folliculitis usually occurs in patients with existing acne, the development of this new process is often mistaken as an exacerbation of acne.

The morphology of the lesions is as follows:

  • Type 1 (approximately 80% of patients) - Superficial pustular lesions without comedones

  • Type 2 (approximately 20% of patients) - Deep, nodular, and cystic lesions

The distribution of the lesions is extending from the infranasal area to the chin and the cheeks.

Complications of gram-negative folliculitis are largely limited to expansion of infection, as well as potential permanent scarring. Of note, however, is the high potential for this condition to be missed when a diagnosis is attempted through telemedicine or direct-to-consumer telemedicine websites and smartphone apps. [3]

Diagnostics

Also see Workup.

In contrast to typical acne lesions, lesions of gram-negative folliculitis do not contain a comedonal core. A minimal amount of keratinous material is present in an intrafollicular sea of pus. Occasionally, segments of the follicular wall may be dissolved. Organisms are located in nests around clumps of keratinous material, around hairs, and in phagocytes. In contrast to the predominant gram-negative rod recovered on culture, Gram stain of the tissue section may show a mixed flora (ie, gram-positive rods and cocci, gram-negative rods, budding yeasts).

Management

Also see Medication.

Treatment of gram-negative folliculitis includes the use of isotretinoin and systemic antibiotics. [4]

Isotretinoin offers the most effective cure for gram-negative folliculitis. [5, 6, 7]  It is a synthetic beta-carotene derivative that is highly effective when used in patients with severe nodulocystic acne unresponsive to conventional therapy. Studies in patients with gram-negative folliculitis have demonstrated effective eradication of facial lesions and nasal carriage with isotretinoin, with an average clearance time of approximately 2-3 months. A low incidence of recurrence has been reported with this therapy. Isotretinoin has no antibiotic effect against the organisms causing gram-negative folliculitis. Several mechanisms have been proposed for its action, including sebum suppression, because all patients with this disease have severe seborrhea prior to isotretinoin treatment, and drying out of the mucous membranes, including the nasal mucosa, which is the reservoir for the organisms.

Systemic antibiotics were the mainstay of therapy for gram-negative folliculitis prior to the development of isotretinoin; the choice of antibiotic was dictated by antibiotic sensitivities. Topical therapy rarely works. The most effective antibiotics have come from the bacteriostatic group, which includes ampicillin and trimethoprim-sulfamethoxazole. Reports have conflicted concerning the degree to which these medications can eradicate the carriage of gram-negative organisms and induce remission. Most studies describe recurring infection after therapy is discontinued, making antibiotic use largely a suppressive modality.

Gram-negative folliculitis caused by Pseudomonas organisms in whirlpools usually subsides spontaneously within 10 days without recurrence. In patients with facial folliculitis caused by Pseudomonas organisms associated with acne vulgaris, the infection clears when the source of the organism, external otitis, is cured. Acinetobacter baumannii folliculitis in the setting of AIDS has responded to intravenous treatment with ticarcillin-clavulanic acid.

Most patients have ordinary acne in addition to gram-negative folliculitis. Once the folliculitis has responded, residual acne must be treated by other methods, including retinoic acid, benzoyl peroxide, cryotherapy, and other therapies.

Gram-negative folliculitis is relatively uncommon, and the general benefit from antibiotics far outweighs the occasional complication of folliculitis.

Curcumin-mediated antimicrobial photodynamic therapy (aPDT) is a promising therapeutic option if the folliculitis is due to P. aeruginosa; the adjuvant effect of polymyxin B on the antibacterial activity of curcumin-mediated aPDT may also be useful. [8]

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Pathophysiology

The anterior nares serve as a reservoir of gram-negative organisms. Prolonged systemic antibiotic treatment can alter the relative prevalence of bacterial flora carried in the nasal passages. An inverse relationship has been demonstrated between the presence of gram-positive organisms and gram-negative organisms in the pharyngeal, axillary, and toe-web flora. In patients with acne who are treated with oral antibiotics, the number of Staphylococcus aureus organisms and diphtheroids decreases and the number of coagulase-negative staphylococcal and enterobacterial organisms increases in the nose. Usually, gram-negative bacteria constitute less than 1% of the total bacterial flora in the nose. In patients with gram-negative folliculitis, enterobacteria constitute approximately 4% of the total bacterial flora.

The antibiotic-induced increase in gram-negative organisms usually does not result in adverse effects, and once antibiotic treatment is discontinued, the nasal flora reverts to its previous state. However, in a small number of patients, the increased number of gram-negative organisms results in a transfer of organisms to neighboring areas of the face. The bacteria populate existing acne lesions and can also cause pustules to arise de novo.

In addition to the need for suppression of interspecies interference, gram-negative organisms require a sufficiently moist environment to survive and proliferate. The presence of excessive seborrhea may promote the survival of gram-negative bacteria by trapping moisture in the face. The effectiveness of isotretinoin in the treatment of gram-negative folliculitis has been attributed to its ability to make the skin and the mucous membranes dry as a result of the marked reduction in sebaceous gland secretion.

Another factor has been implicated in the pathogenesis of gram-negative folliculitis. An assessment of hypersensitivity reactions to various microbial recall antigens and granulocyte functions was performed. Lowered serum concentrations of immunoglobulin M (IgM) and alpha1-antitrypsin and elevated levels of immunoglobulin E (IgE) were found, suggesting that altered immunologic factors may play a critical role in the pathogenesis of gram-negative folliculitis.

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Etiology

Systemic antibiotics, such as tetracyclines, can alter the nasal flora. The resultant overgrowth of gram-negative bacteria can lead to folliculitis.

Type 1 lesions are usually associated with a lactose-fermenting, gram-negative rod, including Klebsiella, Escherichia, and Serratia species. Cases associated with Citrobacter and Morganella species, other organisms of the Enterobacteriaceae family, have also been described. [9, 10, 11]

Type 2 lesions are associated with Proteus species. These species are motile and, thus, have the ability to invade more deeply, producing the large suppurative abscesses that result in deeper cystic lesions.

Folliculitis caused by Pseudomonas organisms is typically associated with immersion in hot tubs and swimming pools, resulting in a generalized folliculitis. [12] Aeromonas hydrophila has also been associated with water sources, including an inflatable pool. [13, 14] Home spas have also been implicated in causing gram-negative folliculitis. In the reported patients who were swimmers, a sudden unmanageable flare-up of facial acne associated with chronic bilateral otitis externa was reported. A case of Acinetobacter baumannii folliculitis of the face, neck, arms, and upper part of the trunk has been reported in a patient with AIDS. [15]

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Epidemiology

US frequency

Gram-negative folliculitis is a relatively uncommon complication of prolonged antibiotic therapy. In two studies, approximately 4% of patients with acne vulgaris who were under treatment with broad-spectrum antibiotics reported this infection. However, the frequency of this infection is probably generally underestimated because clinicians rarely perform correct sampling and bacteriology.

Race-, sex-, and age-related information

No racial or sexual predilection is documented for gram-negative folliculitis.

Although gram-negative folliculitis is largely a complication of acne vulgaris and thus is expected to follow the age distribution of that entity, a slightly increased age at onset has been observed. The tendency for gram-negative folliculitis to begin after the early teenage years is most likely because most patients who develop gram-negative folliculitis have undergone treatment of acne with a broad-spectrum antibacterial agent for a prolonged period.

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Prognosis

Gram-negative folliculitis has no associated increase in mortality. Morbidity is related to local pain and to the unwanted cosmetic effect of the folliculitis. Complete remission of the gram-negative folliculitis results with isotretinoin use. If antibiotic therapy is used, long-term suppression is required.

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Patient Education

Educate patients that gram-negative folliculitis is a different disease entity and that the treatment of the primary disease (acne or rosacea) is causing the gram-negative folliculitis. If antibiotic therapy is used, make patients aware that treatment is usually only suppressive.

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