Skin manifestations of malnutrition in HIV-positive meningitis patients

HIV infection and meningitis are diseases which are known to precipitate malnutrition. Skin manifestations of malnutrition are easy to identify. We tried to describe the skin manifestations of malnutrition in HIV-positive patients with meningitis. Patients included in the study were from a tertiary referral hospital in South India. In a cross-sectional observational design, we studied 56 adult [> 14 years] HIV-seropositive patients with meningitis by clinical assessment of skin manifestations of malnutrition. Skin wasting (31.5%), hyperpigmentation of skin (22.2%) and skin ulceration (16.4%) were the chief skin manifestations of malnutrition in HIV-positive patients with meningitis. Our study shows that certain cutaneous features of malnutrition like skin ulcers, skin wasting and hypo pigmentation are common in HIV patients with meningitis.


Introduction
Malnutrition is common in patients with HIV infection. This may be due to decreased nutrient intake, impaired nutrient absorption, changes in metabolism, and increased requirements of energy, protein, vitamins and minerals (Shenkin 2006). It is also due to the high predisposition of these individuals to a myriad of infections such as chronic infections like tuberculosis, fungal infections, and gastrointestinal diseases like diarrhoea and malabsorption syndromes.
The malnutrition thus accrued by these patients, contributes to immune impairment, making the body further vulnerable to frequent illnesses (Duggal et al. 2012). One of the severe illnesses in HIV-infected individuals is meningitis. The involvement of the CNS in meningitis decreases appetite and makes the patients incapable of feeding themselves. Parenteral nutrition is not wholly adequate in most of these patients (Bari et al. 2016). Given that HIV-infected patients are more commonly affected by chronic meningitis with a protracted course, the risk for malnutrition is even higher in this group of individuals.
Malnutrition has been reported in a high proportion of patients with both HIV infection and meningitis. Previous studies have shown lower BMI, decreased body weight and low mid-arm circumference in these patients (dos Santos and Almeida 2013;Hossain et al. 2009). But overt features of malnutrition of the surface organs such as the skin, hair and nails have scarcely been reported. A study of these features that can be easily observed by clinical examination can identify markers for malnutrition in this vulnerable group.
Only by identifying these features can the causes be ascertained and targeted therapies be planned. With this view, we describe the observed features of skin manifestations of malnutrition in HIV-positive patients with meningitis in a tertiary hospital.

Methods
The Government General Hospital, Guntur is a tertiary referral centre for 20 million people. It is located in the centre of Andhra Pradesh, a state in South India. It has 1200 beds catering to a large semi-urban and rural population. We took up a cross-sectional observational study in this setting from January 2017 to January 2019. We recruited 63 adult [> 14 years] HIV-infected patients who presented with meningitis. 45 HIV-seropositive patients without meningitis and 56 HIV-seronegative meningitis patients were considered as controls. The HIV status of the patients was confirmed in the hospital by standard protocols. Patients tested positive with antibody strip method were confirmed by ELISA and Western blot methods ("WHO | Diagnosis of HIV infection in infants and children," n.d.). Clinical diagnosis of meningitis was based on the presence of a combination of fever, headache, altered sensorium, neck rigidity and signs of meningeal irritation. Confirmation of the diagnosis and identification of the etiological agent was done as per standard guidelines. Diagnosis was based on clinical presentation, past or contact history of tuberculosis, CSF lymphocyte count, glucose, protein, neuroimaging findings like obstructive hydrocephalus, infarcts, smear stain and culture and PCR. (Marais et al. 2010;Brouwer et al. 2004;van Ettekoven et al. 2017;Kupila et al. 2006). Written informed consent was taken from the patient or the next of kin in case of ill patients. The institutional ethics committee at Guntur Medical College, Guntur (GMC/IEC/033/2017) approved the study protocol.
In these patients, manifestations of malnutrition in the skin, hair and nails were noted. These features were as follow: Skin ulcers-round or oval ulcers with sharp borders, deep bases with minimal surrounding inflammation (Galimberti and Mesinkovska 2016) Skin wasting-thin shiny skin with sparse hair (Galimberti and Mesinkovska 2016)

Results
We included 56 HIV-seropositive patients diagnosed with meningitis out of 63 recruited. Seven patients were excluded due to inadequate data. The mean age of our patients was 35 ± 9 years, of which 32.1% were women (Table 1).
In the 45 HIV-seropositive group without meningitis, the mean age was 31 ± 2 years, of which 22% were women. We found skin wasting in 11.7% of the patients and hyperpigmentation of skin in only 2.3%. In the 56 HIV-seronegative meningitis patients, the mean age was 40 ± 3 years, of which 36% were women. We found no skin manifestations of malnutrition.

Discussion
In our study, HIV-positive meningitis patients were found to have certain cutaneous features of malnutrition such as skin ulceration, skin wasting and hyperpigmentation of the skin.
Such skin disorders are reported in over 90% of HIV-infected people in other clinical studies (Innocenzi 2001). The mechanisms underlying are manifold.
Firstly, HIV patients are commonly undernourished. HIV-seropositive individuals have reduced food intake, poor absorption of nutrients and abnormal metabolism (Shenkin 2006). This results in chronic malnourishment in these people. Since malnutrition is also an important detriment to the integrity of the integument, skin wasting is more common in HIV patients than normal age-and sexmatched people. These individuals thus have dry, atrophic skin prone to peeling and ulceration (Stefanaki et al. 2002;Zaidi and Lanigan 2010). Secondly, HIV itself destroys the skin cells especially the Langerhan cells (Cedeno-Laurent et al. 2011). And thirdly, the presence of the virus in the body increases inflammatory cytokines in the circulation (Sokoya et al. 2017). These pro-inflammatory chemicals are harmful to the skin. As such, damage to the skin is more common in HIV individuals. Invariably, at some time in their illness, these patients manifest overt skin changes (Innocenzi 2001).
An easily perceived change in the skin is altered pigmentation. Hyperpigmentation of the skin is common in HIV patients (Singh et al. 2009). It is associated with up to 47% of HIV-infected individuals. It is caused by many nutritional deficiencies especially those of Vitamin C, B12 and Niacin (Galimberti and Mesinkovska 2016). As nutritional deficiencies are common in HIV-infected patients, skin hyperpigmentation is commonly seen in them. Other causes of hyperpigmentation have been proposed in HIV patients. These include ART drugs causing hypersensitivity to sunlight, endocrine system disorders such as adrenal insufficiency and secondary infections causing hyperpigmentation (Jing and Ismail 1999). However, we considered only the characteristic hyperpigmented skin lesions (Galimberti and Mesinkovska 2016) of nutritional deficiency in our study. Hence, our study projects only these changes.
Meningitis in HIV patients is a devastating disease. It is more profound in seropositive individuals than in others (Thinyane et al. 2015). This culminates in the precipitation of a number of factors causing malnourishment which can manifest in the largest visible organ of the human body-the skin. Vomiting and altered sensorium, common features of meningitis in HIV patients, decrease appetite and limit food intake. Cranial nerve palsies causing dysphagia also decrease the nutrient intake. The altered gut absorption (Haussner et al. 2019) and motility further cut down the nourishment. Antibiotic therapy-induced microbiota changes, the increased nutrient utilisation by the chronically overwrought immune system and the disease-induced stress deprive the patient of essential nutrients. This malnourishment is reflected in the changes in the body including the more easily observed parts such as the skin, hair and nails.
The portents of malnutrition observed in our study might also be due to another important factor. Tuberculosis was the most common agent of meningitis in our patients. Tuberculosis is alternatively called consumption for good reason. It seems to consume the patient slowly, i.e. tuberculosis itself causes malnutrition (Ducati   . 2006). This may be one of the reasons for the skin changes observed in this cohort. Even with all these considerations, certain limitations of our study should be borne in mind. For one, 56 subjects is not a very large number of patients. And also, multiple other factors such as the socioeconomic standing of the patients might have affected our results.

Conclusions
Nevertheless, our study shows that certain cutaneous features of malnutrition like skin ulcers, skin wasting and hypopigmentation are common in HIV patients with meningitis. Therefore, these should be looked for by clinicians treating these patients and appropriate nutritional management should also be undertaken.