Experimental Production of Acne, Effect of X-Ray Therapy in Certain Nonmalignant Dermatoses, and Experimental Miliaria

This online-only bonus feature is an ongoing review of past peer review journal articles with significant impact on dermatology.

Emily DothardEmily Dothard, MD

In honor of a dermatologist who made a large impact on the field of dermatology, both in research and education, this resident journal club will feature three of Dr. Walter B. Shelley’s publications. 

The Experimental Production of Acne by Penta- and Hexachloronaphthalenes 

This report details the gross and microscopic observations made with the induction of acne in 31 male subjects after repeated topical naphthalene exposure. Men, aged 25-35, without any clinical evidence of acne, were exposed to a mixture of penta- and hexachloronaphthalenes as a 50% suspension in mineral oil daily for 35 days. This mixture was applied to different areas of the body, including the back, face, leg, axilla, scalp, scrotum, and pinna. Representative biopsy specimens were taken at day 60. Acne developed in all seven regions that the topical naphthalene mixture was applied. The comedone was the first and common finding in all areas. Inflammatory lesions subsequently developed in all areas except the scalp and scrotum. The inflammatory acne that developed in the axilla resembled hidradenitis suppurativa.  The acne that developed on the back was indistinguishable from acne conglobata. Histologic findings confirmed comedone formation within one to three weeks. Additionally, the sebaceous glands were noted to have temporarily disappeared in the majority of the specimens, likely related to follicular occlusion. The development of inflammatory lesions was marked by destruction of the follicular wall with the outpouring of the follicular contents into the dermis, leading to abscess formation. The authors discuss that this phenomenon of the development of acne related to exposure of chlorinated naphthalene had been described previously and termed “chloracne.” However, experimental studies were limited at the time Dr. Shelley’s report was published. Based on the observations of this study, Dr. Shelley and his coauthor, Dr. Albert Kligman, conclude that chloracne appears to be a chemical dermatosis due to a primary toxic effect of the chloronaphthalene. 

Reference: Shelley WB, Kligman AM. The experimental production of acne by pentaand hexachloronaphthalenes. AMA Arch Derm. 1957 May;75(5):689-95. PubMed PMID: 13410133.


A Controlled Clinical Study of the Effect of X-Ray Therapy in Certain Nonmalignant Dermatoses

In this study, Dr. Shelley and coauthor, Dr. John Crissey, described the efficacy of radiation therapy in nonmalignant dermatoses. Subjects with lichen simplex chronicus, lichen planus, nummular eczema, contact dermatitis, and acne vulgaris were selected for treatment. Patients received weekly radiation treatments of 90KV in doses of 100 r for four weeks regardless of disease state or type. A coned area was treated and the diseased areas outside of the radiation cone that were not treated were considered the control. Two types of responses were observed. Lichen simplex chronicus, lichen planus, and psoriasis demonstrated a consistent and significantly greater response within the radiated area than the control. However, areas treated with psoriasis quickly recurred in several patients. The authors argue that given the chronicity of psoriasis, there is little argument for the use of radiation therapy in psoriasis. In the case of nummular eczema, contact dermatitis, and acne, steady progression toward healing in both radiated and control areas was noted, with small but detectable differences between the two areas. Despite demonstration of a favorable response, the authors argue this is not necessarily an indication for use of radiation in these nonmalignant dermatoses. However, they argue, evidence regarding treatment efficacy is an important part of disease management. 

Reference: Crissey JT, Shelle WB. A controlled clinical study of the effect of X-ray therapy in certain nonmalignant dermatoses. N Engl J Med. 1952 Dec 18;247(25):965-70. PubMed PMID: 13002656.


Experimental Miliaria in Man 

In this study, Dr. Shelley sought to determine methods of sweat gland obstruction via iontophoresis. Thirty-five healthy male subjects were treated with iontophoresis while placed in a thermal cabinet to stimulate sweating. The degree of sweating was graded and biopsies were taken on eight of the subjects. In subjects who did not sweat, there was no change in the local areas treated with iontophoresis. In subjects who did sweat, there was a noticeable difference between the treated and untreated areas with partial to complete anidrosis in treated areas along with few to multiple vesicles. These vesicles disappeared a few hours after cessation of sweating but recurred over the next two to three weeks each time the subject sweat. Histology of post-iontophoresis anhidrotic skin demonstrated small plaques and plugs of hyperkeratotic and parakeratotic stratum corneum at the sweat duct orifices with dilation of the intraepidermal portion of the sweat duct in many cases. Vesicles were present in five of the six biopsies. The gross and microscopic findings were consistent with a miliaria-like reaction. He theorized that this was possible because of the non-specific injury iontophoresis had on the epidermis with which resulted in abnormal keratinization. This abnormal keratinization produces a hyperkeratotic plug which blocks the flow of sweat to the surface of the skin. There is no injury to the sweat duct acini which continue to produce sweat, thus the development of a vesicle ensues. Dr. Shelley’s findings demonstrated that it is possible to induce a miliaria-like eruption secondary to sweat retention anidrosis with one iontophoresis treatment.

Reference: Shelley WB, Horvath PN. Experimental miliaria in man; production of sweat retention anidrosis and miliaria crystallina by various kinds of injury. J Invest Dermatol. 1950 Jan;14(1):9-20, illust. PubMed PMID: 15402164.