AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Gram-negative folliculitis, first described by Fulton et al in 1968, 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. 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.

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.

Recently, 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.

Frequency

United States

Gram-negative folliculitis is a relatively uncommon complication of prolonged antibiotic therapy. In 2 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.

Mortality/Morbidity

Gram-negative folliculitis has no associated increase in mortality. Morbidity is related to local pain and to the unwanted cosmetic effect of the folliculitis.

Race

No racial predilection is documented.

Sex

No sexual predilection is documented.

Age

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 this disease 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.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

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 1 of 2 histories as follows:
• • 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. This exacerbation may occur a few days following cessation of an effective antibiotic or a few days following institution of a new antibiotic.

Physical

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

• Morphology of the lesions
• • Type 1 (approximately 80% of patients) - Superficial pustular lesions without comedones
  • Type 2 (approximately 20% of patients) - Deep, nodular, and cystic lesions
• Distribution of the lesions - Extending from the infranasal area to the chin and the cheeks

Causes

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 species, another organism of the Enterobacteriaceae family, have also been described.
• 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.
• Although almost all lesions have been found to be caused by these organisms, a report of 3 patients with lesions caused by Pseudomonas aeruginosa has been published. No associated carriage was found in the anterior nares. Folliculitis caused by Pseudomonas organisms is typically associated with immersion in hot tubs and swimming pools, resulting in a generalized 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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The diagnosis can often be made based on the history and the physical examination findings alone. However, confirmation with Gram stain and culture is recommended.
• In confirming the diagnosis with Gram stain and culture, use special care in culturing. Gram-negative organisms are sensitive to desiccation; samples must be taken quickly and cultured as soon as possible. The pustule that is sampled should also be fresh. A small pustule on an erythematous base is preferable for culturing purposes.
• Culture pustules in any patient with acne who is in their late teens or older and has been on antibiotics and develops a pustular form of the disease.
• Gram-negative organisms cannot be recovered from every pustule.
• Selective medium-containing dyes, such as methylene blue, allow selective growth of gram-negative organisms while inhibiting growth of gram-positive organisms.
• The organisms that produce colonies on eosin-methylene blue agar are classified as either lactose-fermenting gram-negative rods or Proteus species by their cultural characteristics and their ability to ferment lactose.
• • Lactose-fermenting, gram-negative rods produce small, dark, discreet, metallic colonies.
  • Proteus species produce rapidly spreading, translucent, and odorous colonies.
• In patients with facial folliculitis that presents a diagnostic challenge, a potassium hydroxide mount (10-20% potassium hydroxide is used to stain a sample on a slide and look for possible fungal elements) and a skin biopsy specimen may be of value.

Histologic Findings

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).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

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

• Isotretinoin offers the most effective cure.
  • 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 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. A 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.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Retinoids

These agents modulate keratinocyte differentiation and decrease sebum production.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prognosis

• Complete remission of the disease results with isotretinoin use. If antibiotic therapy is used, long-term suppression is required.

Patient Education

• Teach patients that the lesions of gram-negative folliculitis are 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.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize the development of a new process that is exacerbated by continued use of antibiotic therapy is a pitfall.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bachmeyer C, Landgraf N, Cordier F, et al. Acinetobacter baumanii folliculitis in a patient with AIDS. Clin Exp Dermatol. May 2005;30(3):256-8. [Medline].
• Blankenship ML. Gram-negative folliculitis. Follow-up observations in 20 patients. Arch Dermatol. Oct 1984;120(10):1301-3. [Medline].
• Boni R, Nehrhoff B. Treatment of gram-negative folliculitis in patients with acne. Am J Clin Dermatol. 2003;4(4):273-6. [Medline].
• Chastain MA. A cycle: recurrent gram-negative folliculitis with Citrobacter diversus (koseri) following eradication of recurrent staphylococcal pyoderma. Arch Dermatol. Jun 2000;136(6):803. [Medline].
• Fulton JE Jr, McGinley K, Leyden J, Marples R. Gram-negative folliculitis in acne vulgaris. Arch Dermatol. Oct 1968;98(4):349-53. [Medline].
• James WD, Leyden JJ. Treatment of gram-negative folliculitis with isotretinoin: positive clinical and microbiologic response. J Am Acad Dermatol. Feb 1985;12(2 Pt 1):319-24. [Medline].
• Leyden JJ, Marples RR, Mills OH Jr, Kligman AM. Gram-negative folliculitis--a complication of antibiotic therapy in acne vulgaris. Br J Dermatol. Jun 1973;88(6):533-8. [Medline].
• Leyden JJ, McGinley KJ, Mills OH. Pseudomonas aeruginosa gram-negative folliculitis. Arch Dermatol. Oct 1979;115(10):1203-4. [Medline].
• Maples RV. Bronchodilator response in COPD. Am Rev Respir Dis. Sep 1986;134(3):634-5. [Medline].
• Marples RR, Fulton JE, Leyden J, McGinley KJ. Effect of antibiotics on the nasal flora in acne patients. Arch Dermatol. Jun 1969;99(6):647-51. [Medline].
• Mostafa WZ. Citrobacter freundii in gram-negative folliculitis. J Am Acad Dermatol. Mar 1989;20(3):504-5. [Medline].
• Neubert U, Jansen T, Plewig G. Bacteriologic and immunologic aspects of gram-negative folliculitis: a study of 46 patients. Int J Dermatol. Apr 1999;38(4):270-4. [Medline].
• Noble WC. Gram-negative bacterial skin infections. Semin Dermatol. Dec 1993;12(4):336-41. [Medline].
• Plewig G, Nikolowski J, Wolff HH. Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol. Apr 1982;6(4 Pt 2 Suppl):766-85. [Medline].
• Simjee S, Sahm DF, Soltani K, Morello JA. Organisms associated with gram-negative folliculitis: in vitro growth in the presence of isotretinoin. Arch Dermatol Res. 1986;278(4):314-6. [Medline].
• Tan HH. Antibacterial therapy for acne: a guide to selection and use of systemic agents. Am J Clin Dermatol. 2003;4(5):307-14. [Medline].
• Tarlow MM, Piela Z, Schwartz RA. Gram-negative folliculitis - a diagnostic challenge. Dermatologia Kliniczna. 2002;4:7-9.

Article Last Updated: Jan 24, 2007