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Contemplating the association of hydrochlorothiazide to nonmelanoma skin cancer raises my blood pressure


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By Warren R. Heymann, MD
March 29, 2018

hydrochlorothiazide
Photosensitivity secondary to hydrochlorothiazide (HCTZ) use. Well-demarcated erythema on sun-exposed region of the forearm of this patient who was taking HCTZ.
Credit: JAAD

Cellophane, Mister Cellophane
Should have been my name, Mister Cellophane
‘Cause you can look right through me
Walk right by me and never know I’m there

If a rash could commiserate with Amos, the accused murderess Roxie Hart’s husband in the musical Chicago, Pityrosporum folliculitis (PF) would be a leading candidate. I have diagnosed it, but how many times have I missed it?

(Most authorities suggest that the preferred term for PF is Malassezia folliculitis [MF]. Both terms PF and MF will be used synonymously in this commentary.)

Nearly half a century ago, Weary et al reported the case of a 36 year-old woman with an acneiform eruption composed of uniform small follicular papules and pustules, surrounded by a rim of erythema, distributed symmetrically over her upper trunk, abdomen, neck and face. She had 5 episodes of the rash, each induced by oral antibiotics, including tetracycline. The lesions would resolve upon discontinuation of the antibiotics. Cultures demonstrated Pitrosporum orbiculare, and one culture a coryneform organism. The authors hypothesized that antibiotics altering the follicular microbiologic equilibrium could have been pathogenic. (1)

Potter et al propagated the concept of PF in a report from the Skin and Cancer Hospital in Philadelphia, in a clinical-pathologic study of 7 cases. The authors surmised that the oval, PAS-positive budding yeasts were actually pathogenic in patients with folliculitis, not just as present cutaneous commensal organisms. They also noted that only spores, (no hyphae, as seen in tinea versicolor) were observed. (2)

Early in my career, there were heated discussions among the cognoscenti as to whether PF was a distinct entity. I became an ardent believer after seeing a dramatic case in a 37 year-old pregnant woman with a prior history of acne vulgaris. (3)

The genus Malassezia now includes 14 species of basidiomycetous yeast (a basidium is a club-shaped spore-bearing structure), of which 9 are human flora. (4) The predominant species in MF are M. restricta, M. globosa, and M. sympodialis. Presumably, the free fatty acids hydrolyzed from triglycerides by Malassezia induce the inflammatory response. Aside from antibiotics, predisposing factors for MF include HIV infection, administration of corticosteroids, or the use of other immunosuppressive agents. It is also speculated that steroid folliculitis (which also presents as monomorphous papulopustules) may be MF. (5)

Prindaville et al performed a retrospective review of patients aged 0 to 21 years old with Pityrosporum folliculitis confirmed by a potassium hydroxide preparation. Of 110 patients, more than 75% had acne that had recently been treated with antibiotics, and when recorded, 65% reported pruritus. Clinical examination demonstrated numerous 1- to 2-mm monomorphic papules and pustules that were typically on the forehead extending into the hairline and on the upper portion of the back. ] Interestingly, only 15% had associated seborrheic dermatitis and only 4% had tinea versicolor. More than half (54%) had prior acne treatment – I was surprised that 48% of these patients received cephalexin, with only 22% utilizing doxycycline and 21% minocycline. The authors emphasized that PF is often pruritic and persists, or worsens, despite the use of antibiotics targeting Proprionobacterium acnes. Their patients responded well to topical agents such as ketoconazole shampoo. Some cases required oral therapy. (6) Fluconazole is appropriate because oral ketoconazole is no longer recommended for superficial fungal infections because of the risk of hepatic or adrenal injury.

While most astute dermatologists will diagnose characteristic cases of MF, atypical cases may not be considered in a differential diagnosis. In their series of 94 patients, Tsai et al reported that 22 (23%) were considered atypical, often presenting as eosinophilic folliculitis/rosacea-like lesions on the face or pityriasis lichenoides/prurigo-like lesions of the trunk and extremities. (7)

Potter et al were absolutely correct in stating: “Pityrosporum folliculitis is probably quite common. It is reasonable to assume that most cases pass unrecognized and are misdiagnosed as an acneiform eruption and treated accordingly.” (2) When your acne patients are not improving, do a careful clinical exam. Make sure your patient is not a cellophane man – if the lesions itch and appear as monomorphous papulopustules on the head, neck, upper trunk and arms, consider a KOH or biopsy with a PAS stain.

1. Weary PE, et al. Acneform eruption resulting from antibiotic administration. Arch Dermatol 1969; 100: 179-83.
2. Potter BS, et al. Pityrosporum folliculitis. Report of seven cases and review of the Pityrosporum organism relative to cutaneous disease. Arch Dermatol 1973; 107: 388-91.
3. Heymann WR, Wolf DJ. Malassezia (Pitysporon) folliculitis occurring during pregnancy. Int J Dermatol 1986; 25: 49-51.
4. Prohic A, et al. Malassezia species in healthy skin and in dermatological conditions. Int J Dermatol 2016; 55: 494-504.
5. Harada K, et al. Malassezia species and their associated skin diseases. J Dermatol 2015; 42: 250-7.
6. Pridaville B, et al. Pitrosporum folliculitis: A retrospective review of 110 cases. J Am Acad Dermatol 2018; 78: 511-4.
7. Tsai Y-C, et al. Atypical clinical presentations of Malassezia folliculitis: A retrospective analysis of 94 biopsy-proven cases. Int J Dermatol 2018; 57: e19-20.


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