Are You Confident of the Diagnosis?
What you should be alert for in the history
Many patients with acne and rosacea are treated with long-term systemic antibiotics. On occasion, this can cause a shift in the gram-positive flora in the nares and facial skin to gram-negative bacteria such as Escherischia coli, Pseudomonas aeruginosa, Serratia marescens, Klebsiella species, Citrobacter species, and Proteus mirabilis. While infrequent, this shift in flora can result in a transfer of the gram-negative organisms to other areas of the face, causing a new outbreak or flare of existing acne.
Gram-negative folliculitis can also occur with hot tub or spa use, and is most commonly caused by Pseudomonas aeruginosa; however, there are recent reports of Aeromonas hydrophila causing a similar eruption. In patients with human immunodeficiency virus (HIV) infection, gram-negative folliculitis caused by Acinetobacter baumannii has been reported.
Characteristic findings on physical examination
Gram-negative folliculitis can be divided into two main categories. Type 1 lesions are seen in 80% of the cases and appear as superficial pustules without the presence of comedonal lesions. Type 2 is characterized by deep nodular or cystic lesions. In approximately 20% of patients, the most common organism isolated is Proteus species.
Other clinical scenarios in which gram-negative folliculitis can be seen are in people with recent exposures to hot tubs or swimming pools; in these situations, the lesions typically appear as diffuse follicular red papules on the trunk. In patients with HIV or acquired immunodeficiency syndrome (AIDS), diffuse acneiform eruptions can sometimes be associated with gram-negative bacteria as well (Figure 1).
While the diagnosis of gram-negative folliculitis can usually be made on history and clinical exam, an aerobic bacterial culture should be obtained to confirm the diagnosis. A fresh pustule makes the best sample.
Because of the presence of this condition in patients with existing acne, it can easily be overlooked or attributed to a flare of their underlying condition. It is important to think about this clinical entity when patients have a sudden flare or worsening of their acne, or when they are not responding to therapy, especially if they have been treated with long-term systemic antibiotics.
Who is at Risk for Developing this Disease?
Gram-negative folliculitis is seen in 4% of patients who are on systemic antibiotics for a prolonged period. It can also been seen in those who have had recent exposure to hot tubs or spas. The condition has also been reported in patients with HIV or AIDS.
What is the Cause of the Disease?
Typically, gram-positive organisms, such as coagulase-negative Staphylococcus species and aerobic diptheroids, populate the nasal passages, while gram-negative bacteria make up less than 1% of normal flora. In patients receiving long-term antibioitics for acne vulgaris, the nasal flora can be altered, and gram-negative bacteria can flourish. A carrier state for the gram-negative bacteria occurs, which can then disseminate to other sites, leading to the development of gram-negative folliculitis.
Hot tub folliculitis is seen after exposure to contaminated swimming pools or hot tubs. Immunocompromised patients, such as those with HIV or AIDS, can become infected with gram-negative bacteria; however, the source has not been identified in published papers.
Systemic Implications and Complications
Gram-negative folliculitis is confined to the skin and does not have systemic implications or complications in immunocompetent patients.
Treatment options are summarized in Table I.
|Topical Therapy (considered ineffective)||Systemic Therapy|
|Benzoyl peroxide||Isotretinoin 0.5-1.0mg/kg for 20 weeks (treatment of choice)|
|Clindamycin phosphate||Ampicillin 250-500mg every 6 hours (considered supressive)|
|Gentamicin||Trimethoprim-sulfamethoxazole 160/800mg every 12 hours (considered suppressive)|
Optimal Therapeutic Approach for this Disease
The treatment of choice for gram-negative folliculitis is isotretinoin 0.5-1.0mg/kg for 20 weeks. While there are several potential complications, isotretinoin offers the most effective treatment of this condition.
Prior to the availability of isotretinoin, systemic antibiotic therapy was the treatment of choice and was based on culture sensitivities. The most frequently used antibiotics were ampicillin and trimethoprim-sulfamethoxazole. It is generally thought that antibiotic therapy is suppressive in nature, and frequent recurrences are noted after antibiotic therapy is discontinued. Topical medicines are considered ineffective.
Gram-negative folliculitis associated with hot tub use will generally resolve on its own in less than 2 weeks (if the individual stays out of the water source), but can be treated with antibiotics that cover Pseudomonas aeruginosa, including fluoroquinolones.
Patients with HIV/AIDS responded to intravenous ticarcillin-clavulanic acid.
Patients should be advised that topical therapy is generally considered ineffective. Systemic antibiotics can suppress the eruption, but once they are discontinued, relapses are frequent. Since most patients with gram-negative folliculitis have underlying acne vulgaris, the use of isotretinoin can provide a long-lasting cure of both conditions.
While there are several potential complications with isotretinoin therapy, if patients are appropriately educated and followed clinically, it can be a rewarding treatment for patients and physicians alike. Therapy with isotretinoin requires compliance with the iPLEDGE system, which requires monthly visits and education about the potential side effects of isotretinoin therapy. Females require monthly pregnancy tests and the use of two forms of birth control to mitigate the risk of birth defects.
Patients should be warned about the possible increased risk of depression, suicide, and inflammatory bowel disease, although there are no conclusive studies linking these conditions to isotretinoin use. Laboratory monitoring of liver function, a lipid panel, and complete blood count with differential should be checked periodically during therapy.
While bone changes, including hyperostosis, premature epiphyseal closure, and bone demineralization, have been observed with prolonged use or higher dose retinoids, these findings have not been identified with the routine use of isotretinoin, and routine screening is not necessary.
Patients should also be warned of the mucocutaneous side effects associated with isotretinoin use, including dry lips, dry skin, nosebleeds, and the possibility of joint pains, muscle aches, vision changes, and headaches. Patients should also be advised to avoid waxing, laser procedures, chemical peels, and microdermabrasion during isotretinoin therapy.
In cases of hot tub or spa folliculitis, proper spa maintenance is critical. Spa testing strips should be used to ensure proper disinfectant levels. If levels are low, it may be necessary to shock the hot tub. It is also important to periodically clean or change all filters according to the manufacturer instructions. Once hot tub folliculitis has developed, the affected spa should be drained, cleaned with chemical disinfectants, and the filters should be replaced to ensure removal of the offending bacteria.
Unusual Clinical Scenarios to Consider in Patient Management
Gram-negative folliculitis can be a difficult diagnosis to make, and is probably under-reported because routine cultures are rarely performed. Consider this diagnosis if a patient has been on tetracycline antibiotics for 3-6 months with no clinical improvement or if there is a sudden flare of pustular acne or nodulocystic acne during treatment.
What is the Evidence?
Fulton, JE, McGinley, K, Leyden, J, Marples, R. “Gram-negative folliculitis in acne vulgaris”. Arch Dermatol. vol. 98. Oct 1968. pp. 349-53. (This is the first paper describing gram-negative folliculitis. It reviews the basic pathophysiology and clinical scenarios in which it is seen. Much of what is reported in this paper has not changed since 1968, except the advent of isotretinoin as the treatment of choice.)
Mostafa, WZ. “Citrobacter freundii in gram-negative folliculitis”. J Am Acad Dermatol. vol. 20. 1989. pp. 504-5. (This paper describes the addition of Citrobacter freundii to the organisms that can cause gram-negative folliculitis but were not previously reported.)
Mulholland, A, Yong-Gee, S. “A possible new cause of spa bath folliculitis: Aeromonas hydrophila”. Australas J Dermatol. vol. 49. 2008. pp. 39-41. (This reference describes the development of hot tub folliculitis from Aeromonas hydrophila. This possible cause had not been previously reported.)
Bachmeyer, C, Landgraf, N, Cordier, F, Lemaitre, P, Blum, L. “Acinetobacter baumanii folliculitis in a patient with AIDS”. Clin Exp Dermatol. vol. 30. 2005. pp. 256-8. (This reference describes the development of gram-negative folliculitis from Acinetobacter baumanii in AIDS patients.)
Blankenship, ML. “Gram-negative folliculitis. Follow-up observations in 20 patients”. Arch Dermatol. vol. 120. Oct 1984. pp. 1301-3. (In this paper, the author reports the follow-up of twenty patients with gram-negative folliculitis. It describes their clinical presentations, treatments, and follow-up over a 4-48-month period.)
Böni, R, Nehrhoff , B. “Treatment of gram-negative folliculitis in patients with acne”. Am J Clin Dermatol. vol. 4. 2003. pp. 273-6. (This paper reviews the use of isotretinoin as the treatment of choice in gram-negative folliculitis. It provides optimal dosing and length of treatment for complete clearance and also provides a succinct review of the pathophysiology of the disease and clinical scenarios to be aware of.)
Strauss, JS, Krowchuk, DP, Leyden, JJ, Lucky, AW, Shalita, AR, Siegfried, EC. “American Academy of Dermatology/American Academy of Dermatology Association. Guidelines of care for acne vulgaris management”. J Am Acad Dermatol. vol. 56. 2007 Apr. pp. 651-63. (The article cited above contains consensus group recommendations for acne treatment. The paragraphs about isotretinoin review the common potential risks involved with the use of the drug, as well as the standard of care for patient counseling and monitoring during treatment.)
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