Chloracne


Article Author:
Daniel Schlessinger


Article Editor:
Joel Schlessinger


Editors In Chief:
Ahmad Al Aboud
Jayakar Thomas
Pramod Nigam


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Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
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Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
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Hassam Zulfiqar
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John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
12/16/2018 3:24:59 PM

Introduction

Chloracne is an eruption of blackheads, cysts, and pustules that may occur with over-exposure to halogenated aromatic compounds including chlorinated dioxins and dibenzofurans. Commonly, lesions are located on the cheeks, armpits, groin, and behind the ears. Chloracne is linked to toxic exposure to dioxins including herbicides such as Agent Orange. Presence of chloracne is considered to be a clinical sign of dioxin exposure. The severity follows a typical asymptomatic dose-response relationship curve.[1][2]

Etiology

Chloracne results from direct skin contact with chloracnegens. Ingestion and inhalation are also possible causative routes. Chloracnegens are fat-soluble and persist in the body fat for a long period after exposure.[3][4]

Chloracne is caused by exposure to halogenated aromatic hydrocarbons found in:

  • Fungicides
  • Herbicides
  • Insecticides
  • Wood preservatives

Chloracne is a common skin sign of dioxin poisoning. Responsible chemicals include:

  • Chlornaphthalene
  • Chlorobenzene
  • Polychlorobiphenyls (PCBs)
  • Polychlorinated dibenzo-p-dioxins (PCDDs)
  • Polychlorinated dibenzofurans (PCDFs)
  • Pyrazole derivatives
  • Chlorophenol contaminants
  • Trifluoromethyl

Epidemiology

Chloracne is a rare skin condition although outbreaks may occur with an accidental mass exposure. After World War II, several large accidents resulted from food contamination or occupational exposure in Europe. Massive intoxication from contaminated oils has occurred several times in Asia especially Japan. During the Vietnam War, Agent Orange was used widely, but the real prevalence of chloracne in Vietnam veterans is not known. Part of the problem during the Vietnam war was denial and lack of awareness of the potential toxicity of Agent Orange. Today, the use of polyhydrocarbons containing dioxin is curtailed. Despite the concern over dioxin, government scientists in the United States feel that low levels of dioxin are common in the environment. Further, they state that low levels of these agents do not cause chloracne.[5][6][7][8]

Pathophysiology

Chloracne is an inflammatory condition that occurs due to the persistence of toxic chemical properties. It is believed that the toxin activates a series of receptors promoting macrophage proliferation resulting in neutrophilia and a generalized inflammatory response in the skin. This may be augmented by induction of excess tumor necrosis factor in the blood serum.

Histopathology

Chloracne lesions typically involve the hair follicles, which usually contain keratotic material. Presence of small infundibular cysts is more common than comedones. The sebaceous glands are usually not affected, and metaplasia is uncommon. Occasionally one may see hyperpigmentation of the basal layer of the epidermis. In summary, the chloracne lesion has more infundibular cysts and fewer comedones.

History and Physical

Acute exposure to high levels chemicals may cause systemic symptoms. These include:

  • Gastrointestinal illness
  • Liver dysfunction
  • Pancreatitis
  • Neuropathy

As these systemic symptoms abate, skin changes begin, and then the diagnosis of chloracne is more obvious. The skin changes occur as the chemical begins to redistribute out of the organ systems into the sebaceous (oil) glands.

  • Keratinous plugs in skin pores, forming yellowish cysts and dark pustules with open and closed comedones (whiteheads and blackheads)
  • Uninflamed nodules and cysts
  • Greenish pustular discharge
  • Facial skin lesions appear on the cheeks and behind the ears, extending into the armpits and groin. They may also involve the shoulders and chest, the back, and the abdomen. In advanced cases, the lesions may extend to the arms, thighs, legs, hands, and feet.

Chloracne may not appear for 3 to 4 weeks after toxic exposure. If massive exposure occurs, symptoms may appear within days. 

The lesions are most often seen on the cheeks, behind the ears, in the armpits, and in the groin. Although they resemble acne, the skin is not usually oily; in fact, the oil glands are often smaller than usual.

Other skin problems seen with chloracne include:

  • Sweaty palms and soles (hyperhidrosis)
  • Porphyria cutanea tarda (pigmentation, increased hair growth, and blisters on exposed skin).

Evaluation

History and physical exam provide the starting point for diagnosis. Blood test levels for halogenated aromatic hydrocarbons are not reliable for diagnosis due to redistribution of the chemicals around the body and their metabolism.

The diagnosis is mostly on the grounds of history and physical. Biopsies of affected skin may show a reduction of the normal sebaceous gland density and skin hamartomas. Immunohistochemical tests (e.g., CYP1A1) can be done on the hamartomas to determine up or down-regulation of gene expression to support the clinical diagnosis. Immunohistochemical tests (e.g., CYP1A1) may be performed on the hamartomas to determine up or down-regulation of gene expression to support the diagnosis.

In the past, measurement of polyhydrocarbons routinely was made in the blood and urine, but these are unreliable tests. The reason is that polyhydrocarbon compounds are very fat soluble and immediately dissipate into fatty tissues and the brain. Hence, the levels in the blood and urine will usually be low.

Treatment / Management

Once chloracne is diagnosed, the primary action is to remove the chemical source. Further treatment is symptomatic. Secondary infections may be treated with oral antibiotics or isotretinoin. Comedones and cysts can be punch excised or cauterized. Chloracne is typically highly resistant to any treatment.[9]

The course is highly variable. In some cases the lesions may disappear within two years, however, in other cases, the lesions may be effectively permanent.

These patients must be followed for a long time because the ingested agent may also induce morbidity of many other organs besides the skin. The debate about whether the exposure to these chemicals also causes cancer means that the patient must be examined on a regular basis to ensure that he or she is not developing a malignancy. Countless cases of Agent Orange have resulted in litigation because of poor follow up.

Pearls and Other Issues

Other health problems associated with chloracne include:

  • Abnormal liver function
  • Fatigue and sleep disturbance
  • Nerve conditions (transient peripheral neuropathy, encephalopathy, poor concentration, and depression)
  • High levels of circulating blood fats (hyperlipidemia)
  • Impotence
  • Type 2 diabetes.

The data for an association with other health problems such as congenital disabilities are conflicting. In any case, both partners should be educated on the potential for congenital disabilities. Furthermore, these individuals should have regular blood work to ensure that they are not developing type 2 diabetes or hyperlipidemia. For the most part, the skin lesions will either spontaneously disappear or remain the same. However, regular exams are needed to ensure that they are not turning malignant.

Enhancing Healthcare Team Outcomes

Chloracne is a rare skin disorder but when it presents, it is best managed by a multidisciplinary team that includes poison control, a dermatologist, a biohazard expert and an internist. The condition has been linked to exposure of dioxins and thus the source needs to be identified. Besides the skin, the patient may develop dysfunction of many other organs. The outcomes depend on the extent and duration of exposure.[10][11]

 

 


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Chloracne - Questions

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Which of the following professions is not associated with the development of chloracne?



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A farmer presents with an eruption of blackheads, cysts, and pustules that occur on the cheeks, armpits, groin, and behind the ears. He says that he has been spraying weeds on the back forty. Which of the following diseases is the most likely cause of the patient's condition?



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A middle-aged patient presents with blackheads, cysts, and pustules on the cheeks, armpits, groin, and behind the ears. He sprays bugs for a living. Which of the following is most closely associated with the patient's condition?



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Which of the following is the most accurate statement about chloracne?



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A patient fell into a large vat of an insecticide. Which of the following is expected?



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Exposure to halogenated aromatic hydrocarbon compounds, such as dioxins and dibenzofurans, induces a cutaneous eruption of polymorphous comedones and cysts referred to as chloracne. Which of the following is expected?



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Chloracne - References

References

Kushwaha P,Kumar H,Kulkarni S,Ghorpade A, Chloracne in a Farming Family. Skinmed. 2017     [PubMed]
Malisch R,Denison MS,Fiedler H,Fürst P,Hoogenboom RLAP,Schaechtele A,Schrenk D,van den Berg M, Do PCDD/PCDF standard solutions used in dioxin analysis pose a risk as potentially acutely toxic to lab personnel? Chemosphere. 2017 Oct     [PubMed]
Ju Q,Zouboulis CC, Endocrine-disrupting chemicals and skin manifestations. Reviews in endocrine     [PubMed]
Bock KW, From dioxin toxicity to putative physiologic functions of the human Ah receptor in homeostasis of stem/progenitor cells. Biochemical pharmacology. 2017 Jan 1     [PubMed]
Patterson AT,Kaffenberger BH,Keller RA,Elston DM, Skin diseases associated with Agent Orange and other organochlorine exposures. Journal of the American Academy of Dermatology. 2016 Jan     [PubMed]
Clemens MW,Kochuba AL,Carter ME,Han K,Liu J,Evans K, Association between Agent Orange exposure and nonmelanotic invasive skin cancer: a pilot study. Plastic and reconstructive surgery. 2014 Feb     [PubMed]
Alchorne Ade O,Alchorne MM,Silva MM, Occupational dermatosis. Anais brasileiros de dermatologia. 2010 Mar-Apr     [PubMed]
Pelclova D,Fenclova Z,Urban P,Ridzon P,Preiss J,Kupka K,Malik J,Dubska Z,Navratil T, Chronic health impairment due to 2,3,7,8-tetrachloro-dibenzo-p-dioxin exposure. Neuro endocrinology letters. 2009     [PubMed]
Meulenbelt J,de Vries I, [Toxicity of dioxins in humans]. Nederlands tijdschrift voor geneeskunde. 2005 Jan 22     [PubMed]
Sweeney MH,Calvert GM,Egeland GA,Fingerhut MA,Halperin WE,Piacitelli LA, Review and update of the results of the NIOSH medical study of workers exposed to chemicals contaminated with 2,3,7,8-tetrachlorodibenzodioxin. Teratogenesis, carcinogenesis, and mutagenesis. 1997-1998     [PubMed]
Assennato G,Cannatelli P,Emmett E,Ghezzi I,Merlo F, Medical monitoring of dioxin clean-up workers. American Industrial Hygiene Association journal. 1989 Nov     [PubMed]

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